Carbon Monoxide Protects Against Ischemia-reperfusion Injury in Vitro via Antioxidant Properties

Carbon monoxide (CO) is believed to mediate many of the cytoprotective effects attributed to the activation of heme oxygenase (HO-1), the enzyme responsible for CO production. Recently, the study of CO-releasing molecules (CO-RMs) has provided a new approach for the delivery of CO. In the present study, we examined whether the cardioprotective properties of CO-RM2 in isolated rat hearts subjected to an ischemia-reperfusion (I/R) sequence were associated with the presence of CO. In addition, the antioxidant properties of CO-RM2 were evaluated. In hearts pretreated with CO-RM2, the improvement in contractile function at the end of the reperfusion period after 20 min of global total ischemia w…

Serum brain-derived neurotrophic factor and platelet activation evaluated by soluble P-selectin and soluble CD-40-ligand in patients with acute myocardial infarction

Little is known about the role of neurotrophins (NT) under adult vascular homeostasis in normal and pathological conditions. The NT family, including nerve growth factor and brain-derived neurotrophic factor (BDNF) are expressed in atherosclerotic vessels. Previous studies demonstrated that plasma BDNF levels were increased in the coronary circulation in patients with unstable angina. However, the role of BDNF during the onset and evolution of unstable angina remains to be elucidated. The objective of this study was to evaluate the relationship between BDNF, functional parameters and biological markers associated with inflammatory processes and platelet activation. BDNF serum levels were as…

The emerging role of miRNA-132/212 cluster in neurologic and cardiovascular diseases: Neuroprotective role in cells with prolonged longevity

Abstract miRNA-132/212 are small regulators of gene expression with a function that fulfills a vital function in diverse biological processes including neuroprotection of cells with prolonged longevity in neurons and the cardiovascular system. In neurons, miRNA-132 appears to be essential for controlling differentiation, development, and neural functioning. Indeed, it also universally promotes axon evolution, nervous migration, plasticity as well, it is suggested to be neuroprotective against neurodegenerative diseases. Moreover, miRNA-132/212 disorder leads to neural developmental perturbation, and the development of degenerative disorders covering Alzheimer’s, Parkinson’s, and epilepsy’s …

Prevention of apoptosis by deferoxamine during 4 hours of cold cardioplegia and reperfusion: in vitro study of isolated working rat heart model.

INTRODUCTION: Heart transplantation is often accompanied by multiple functional alterations, especially in reperfusion period. These are probably related to the reactive oxygen species (ROS) formation catalyzed by transition metals such as iron and copper, and thus the preservation time of the donor hearts is limited. Metabolic protection of the heart grafts is a permanent objective of numerous experiments. Recently, an iron chelator deferoxamine (DFX) was proposed as antioxidant agent for storage solutions in heart grafts. Oxidative stress is also known to mediate the apoptotic cell death in different tissues during ischemia-reperfusion. METHODS: The aim of this study was to evaluate a pos…

The Role of Osteoprotegerin and Its Ligands in Vascular Function

International audience; The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular comp…

Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation.

Structural changes of the male rat aorta were followed from birth to old age in male and female rats. In males, the vessel media width and area progressively increase concomitantly with a decrease of nuclei density during ageing, suggesting an hypertrophy of the smooth muscle cells. These correlations were however not evidenced in females. TUNEL-positive cells were found in media of 4 and 6 months in both sexes, mainly on the luminal side and in the adventitia. When biochemical markers were investigated with immunohistochemistry, media was uniformly stained by the anti-vimentin and anti-alpha-smooth actin at all stages investigated. On the contrary, the surface of media stained with anti-de…

Experimental cerebral ischemia in rats increases myocardial vulnerability to ischemia-reperfusion injury ex vivo

IF 15.064 Fait partie de la session : "Myocardial ischaemia reperfusion injury: a proof of concept?"Presenter: A Meloux (Dijon,FR)http://congress365.escardio.org/Session/18961#.WIszi33sbBw; International audience

Late neointimal tissue growth behind the stent after intravascular gamma-radiation.

To determine the nature of the changes of the vascular wall after intravascular brachytherapy in stented arteries leading to incomplete stent apposition.Stents were implanted in the infrarenal aortas of rabbits, and gamma-intravascular brachytherapy (18 Gy) or a sham radiation procedure was immediately implemented. The arteries were harvested at 6 months for histologic analyses.The external elastic lamina area, as well as the vascular wall area behind the stent, were significantly greater in irradiated vs. control arteries (8.94 +/- 0.68 mm2 vs. 6.87 +/- 0.40 mm2 [p0.001] and 1.56 +/- 0.13 mm2 vs. 0.72 +/- 0.07 mm2 [p0.001], respectively). The ratio of the intimal area behind the stent rela…

Genetic and environmental contributions to serum ascorbic acid concentrations: the Stanislas Family Study.

Although numerous environmental factors are documented to influence serum ascorbic concentrations, little is known about the genetic versus environmental contributions to variation of this trait. The aim of this study was to estimate family correlation and, additive genetic heritability and household effects in a variance component analysis for serum ascorbic acid concentrations. In a sample of ninety French families, information was obtained regarding serum ascorbic acid concentrations, usual dietary intake, lifestyle, and other related covariates. Spouse, parent –offspring and offspring –offspring significant correlation coefficients for serum ascorbic acid concentrations, adjusted for ag…

Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?

International audience; Nitric oxide (• NO) is synthetized enzymatically from L-arginine (L-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of L-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH 4) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS…

Growth and differentiation factor 11 (GDF11): Functions in the regulation of erythropoiesis and cardiac regeneration

International audience; Members of the TGF-β superfamily transduce their signals through type I and II receptor serine/threonine kinases. The binding of activins to activin type IIA (ActRIIA) or type IIB (ActRIIB) receptors induces the recruitment and phosphorylation of an activin type I receptor (ALK4 and/or ALK7), which then phosphorylates the Smad2 and Smad3 intracellular signaling proteins. The regulation of members of the TGF-β family is known to be complex, because many proteins able to bind the ligands and inhibit their activities have been identified. Growth and differentiation factor 11 (Gdf11) belongs to the TGF-β family. GDF11, like other members of the TGF-β superfamily, is prod…

Peroxisome proliferator-activated receptor δ (PPARδ) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis

Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied.We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we …

C022 Experimental approaches of oxidative stress and cardiotoxicity associated with anthracyclines administration

The chronic cardiotoxicity of anthracyclines anticancer drugs is one of the main factors which limits their prolonged use. Clinically, this cardiotoxicity results in a cardiomyopathy with irreversible congestive heart failure with high mortality. The molecular mechanisms, which could explain this cardiac toxicity, are complex but seem distinct from the anticancer mechanism. Several hypotheses were advanced, but it appears that the production of reactive oxygen and nitrogen species (RONS) constitutes the common denominator.In a first study, we evaluated the acute effect of epirubicin administration on the evolution of cardiac functional parameters and production of RONS. Isolated perfused ra…

P4613Long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo and on cardio-protective pathways in mice

Abstract Introduction Nutritional disturbances during the postnatal period may be responsible for a predisposition, or “programming”, to increased cardio-metabolic risk and to a progressive alteration of left ventricular contractility in adulthood. This nutritional perinatal programming may also lead to an alteration of cellular pathways involved in cardiac protection, such as the specific RISK and SAFE pathways, highlighted during pre- and post-ischemic conditioning or those of sirtuins (SIRT), histone deacetylases involved in the regulation of essential biological process. Purpose Our aim was to evaluate in mice the impact of postnatal overfeeding (PNOF) on cardiac sensitivity to ischemia…

Atrial fibrillation is associated with a marker of endothelial function and oxidative stress in patients with acute myocardial infarction

IF 4.066; International audience

Effects of exhaustive exersice and vitamin B6 deficiency on free radical oxidative process in male trained rats

44 ref.; International audience

Carbon monoxide: mechanisms of action and potential clinical implications.

International audience; Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of CO can increase under stressful conditions following the induction of HO-1 (heme oxygnase-1), a ubiquitous enzyme responsible for the catabolism of heme. Unlike nitric oxide, which is a free radical, CO does not contain free electrons but may be involved in oxidative stress. The carbonate radical has been proposed to be a key mediator of oxidative damage resulting from peroxynitrite production, likewise, the precursor of the carbonate radical anion being bicarbonate and carbon dioxide. We report herein some of the transcription factors and protein kinases involved …

Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius.

International audience; Aging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substr…

Symmetric dimethylarginine serum level as a new marker of left ventricular ejection fraction in patients with acute myocardial infarction

Purpose: Asymmetric dimethylarginine (ADMA) is a by-product of protein methylation that has been implicated in the prognosis after acute myocardial infarction (MI) and heart failure through Nitric Oxide Synthase (NOS) inhibition. We aimed to investigate whether SDMA – the endogenous symmetrical stereoisomer of ADMA- that has insignificant inhibitory effects on NOS- might be a marker of left ventricular function in acute MI. Methods: Blood samples from 635 consecutive patients hospitalized 1 (23%). Mean LVEF was 55±13%. Mean ADMA, SDMA and L-arg levels were at 0.72±0.42, 0.51±0.44 and 91±54 μmol/L, respectively. Spearman analysis showed that LVEF was correlated negatively with SDMA (r=-0.151…

Interpretation of epicardial mapping by means of computer simulations: Applications to calcium, lidocaine and to BRL 34915

The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' construction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit …

Effects of alterations in sympathetic nervous activity on the severity of reperfusion-induced arrhythmias in anaesthetised rats.

The effects of a number of interventions influencing sympathetic nervous activity on the severity of coronary artery reperfusion-induced arrhythmias in anaesthetised rats have been examined. Noradrenaline (0.1 microgram kg-1 min-1) reduced the mortality that usually occurred as a consequence of ventricular fibrillation. Isoprenaline (5 micrograms kg-1) did not significantly affect the severity of reperfusion-induced arrhythmias, although arrhythmias occurring during the 5-min period of ischaemia were exacerbated. The alpha-adrenoceptor antagonist nicergoline (0.25 and 0.5 mg kg-1 min-1) markedly suppressed both the ventricular tachycardia and fibrillation occurring upon release of the occlu…

GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism

International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin (Ang)-converting enzyme 2 (ACE2), which is highly expressed in host cells. The cytokine storm observed in patients with COVID-19 contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasi…

P1742Experimental ischemic stroke in rats induce myocardial contractile dysfunction in vivo and ex vivo and increase cardiac vulnerability to ischemia-reperfusion injury ex vivo

Prevalence and impact of metabolic syndrome on hospital outcomes in acute myocardial infarction.

The impact of metabolic syndrome after acute myocardial infarction (AMI) has not yet been studied. In a population-based sample of patients with AMI, we sought to determine the prevalence of metabolic syndrome in patients with AMI, its impact on hospital outcomes, and to assess the relative influence of each of the components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III definition of metabolic syndrome on the risk of death and heart failure.A total of 633 unselected, consecutive patients hospitalized with AMI were categorized according to the NCEP ATP III metabolic syndrome criteria (presence of/=3 of the following: hyperglycemia; triglyceride level/=…

Postnatal Overfeeding in Rodents by Litter Size Reduction Induces Major Short- and Long-Term Pathophysiological Consequences

Numerous studies have demonstrated that the early postnatal environment can influence body weight and energy homeostasis into adulthood. Rodents raised in small litters have been shown to be a useful experimental model to study the short- and long-term consequences of early overnutrition, which can lead to modifications not only in body weight but also of several metabolic features. Postnatal overfeeding (PNOF) induces early malprogramming of the hypothalamic system, inducing acquired persisting central leptin and insulin resistance and an increase in orexigenic signals. Visceral white adipose tissue, lipogenic activity, and inflammatory status are increased in PNOF rodents, while brown adi…

Mitochondrial basis of the anti-arrhythmic action of lidocaine and modulation by the n-6 to n-3 PUFA ratio of cardiac phospholipids

The aim of this study was to evaluate the involvement of mitochondria in the mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused according to the working mode using a medium with or without lidocaine 5 μM. They were then subjected to local ischemia (20 min) and reperfusion (30 min). Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. Reperfusing the ischemic area favored the incidence of severe arrhythmias. Lidocaine treatment abolished almost completely reper…

Role of humanin, a mitochondrial-derived peptide, in cardiovascular disorders

The mitochondria produce specific peptides-mitochondrial-derived peptides-that mediate the transcriptional stress response by their translocation into the nucleus and interaction with deoxyribonucleic acid. Mitochondrial-derived peptides are regulators of metabolism. This class of peptides comprises humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides (SHLPs). Humanin inhibits mitochondrial complex 1 activity and limits the level of oxidative stress in the cell. Data show that mitochondrial-derived peptides have a role in improving metabolic diseases, such as type 2 diabetes. Perhaps humanin can be used as a marker f…

Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction.

Objective— Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis. Methods and Results— Blood samples from 249 consecutive patients hospitalized for acute MI <24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA ( R 2 =0. 25). Baseline ADMA levels were higher in p…

P4550Growth differentiation factor 15 as an integrative biomarker of heart failure in patients with acute myocardial infarction

Abstract Background Growth differentiation factor 15 (GDF15), a stress-responsive cytokine member of the transforming growth factor-β family, is an emerging biomarker in cardiovascular (CV) diseases. GDF15 is weakly expressed in normal condition but increased in pathological situations such as inflammation, oxidative stress, and left ventricular remodeling. Recent data suggest GDF15 as a marker in heart failure (HF). Purpose We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI). Methods In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit …

0110 : Experimental cerebral ischemia in rats increases myocardial vulnerability to ischemia-reperfusion injury ex vivo

For years, the relationship between cardiac and neurological ischemic events has been mainly attributed to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic alterations of cardiovascular function. The aim of this work was to evaluate how prior cerebrovascular lesions affect myocardial function in vivo and ex vivo , as well as myocardial vulnerability to ischemic injury. Cerebral embolization was performed in adult Wistar male rats by the injection of microspheres into the left internal carotid artery. Left ventricular function, investigated in vivo using echocardiography (1 hour, 24 hours and 7 days after the embolization), was not …

Anti-Aging Effects of GDF11 on Skin

International audience; Human skin is composed of three layers: the epidermis, the dermis, and the hypodermis. The epidermis has four major cell layers made up of keratinocytes in varying stages of progressive differentiation. Skin aging is a multi-factorial process that affects every phase of its biology and function. The expression profiles of inflammation-related genes analyzed in resident immune cells demonstrated that these cells have a strong ability to regenerate adult skin stem cells and to produce endogenous substances such as growth differentiation factor 11 (GDF11). GDF11 appears to be the key to progenitor proliferation and/or differentiation. The preservation of youthful phenot…

Glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy

Objective: We assessed the effects of glucose–insulin–potassium (GIK) by echocardiography in stable patients with ischemic dysfunction. Methods: Twelve male patients with stable coronary disease (SCD) and ejection fraction (EF) <45% were studied for systolic function. GIK (glucose 30%, 300 insulin units and KCl 6 g/l) was infused at 1 ml/kg per h over 20 min. Hemodynamic and echocardiographic measurements were recorded at rest (T0), at the end (20 min) of GIK infusion (T + 20), 20 and 40 min after the end of the infusion (T + 40 and T + 60). Results: At T + 20, a significant decrease in WMSI (wall motion score index) was observed compared with T0 (2.16±0.14 vs. 2.30±0.16: P<0.05). An increa…

0201: Cardiac surgery associated with cardiopulmonary bypass in patients with stable coronary disease: growth differentiation factor-15 (GDF- 15) as a predictive factor of adverse events?

BackgroundGrowth differentiation factor-15 (GDF-15) has been identified as a strong marker for cardiovascular disease; however, no data are available concerning the role of GDF-15 in the occurrence of organ dysfunction during cardiac surgery associated with cardiopulmonary bypass (CPB).MethodsThirty four patients, programmed to have non-urgent coronary artery bypass grafting (CABG), were included in our study. Arterial blood samples were taken sequentially from anesthesia induction (IND) until 24h after arrival at the cardiovascular intensive care unit (ICU). Plasma levels of GDF-15, follistatin-like 1 (FLST1), myeloperoxidases (MPO), hydroperoxides and plasma antioxidant status (PAS) were …

In senescence accelerated mouse (SAM) heart, the protective effect of postconditioning is associated with a decrease in oxidative stress

Supplément vol.27, World Congress of Cardiology 2006; International audience; The senescent heart susceptibility to ischemia (I) triggers multiple processes especially oxidative stress but precise mechanisms remain unclear. New animal’s models such as "Senescence Accelerated Mouse" Prone 8 (SAM-P8) and their control (SAM-R1) can be useful for a better understanding of aging process. We studied heart adaptation of these mice to I/reperfusion (R) sequence and a putative cardioprotector effect of post-conditioning (PC). Isolated working mice (8 months) hearts were subjected to a global total ischemia (20 minutes at 38°C), followed by 40 minutes of reperfusion. 4 groups of hearts were constitut…

1203Post-ischemic stroke-induced myocardial dysfunction is associated with nitro-oxidative stress and sympathetic overactivity

P4573In patients with acute myocardial infarction, PCSK9 levels do not predict severity and recurrence of cardiovascular events

Abstract Background In patients with coronary artery disease (CAD), it remains unclear whether serum PCSK9 levels can predict the severity of the disease and the risk of future cardiovascular events. Methods Among the patients admitted for an acute myocardial infarction (MI) from September 2015 to December 2016 in an intensive care unit from a university hospital, serum PCSK9 levels were measured on admission in patients not previously receiving statin therapy. We aimed to evaluate the association between PCSK9 levels, metabolic parameters, severity of CAD on coronary angiography, and the risk of in-hospital events and at one-year follow-up. Results In a total of 648 patients (mean age: 66 …

Prévention de la cardiotoxicité des anthracyclines : approche fondamentale des mécanismes mis en jeu ; relations avec les données cliniques

Resume La cardiotoxicite des agents antitumoraux tels que les anthracyclines est un des principaux facteurs limitant leur utilisation prolongee. Cliniquement elle se traduit par une cardiomyopathie conduisant a une insuffisance cardiaque (IC) congestive irreversible, dont la mortalite est elevee. Les mecanismes moleculaires qui pourraient expliquer la toxicite cardiaque sont complexes mais semblent distincts du mecanisme anticancereux. Plusieurs hypotheses ont ete avancees mais il apparait que l'induction d'un stress oxydatif au sein du tissu myocardique constitue le denominateur commun de ces mecanismes. La prevention de cette cardiotoxicite repose sur une surveillance cardiaque etroite, l…

Protective Effects of a Discontinuous Treatment with Alpha-Lipoic Acid in Obesity-Related Heart Failure with Preserved Ejection Fraction, in Rats

Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group (n = 6) or subjected to abdominal aorti…

Association between Serum Osteoprotegerin Levels and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction

International audience; Background. Osteoprotegerin (OPG), a glycoprotein of the tumour necrosis factor (TNF) superfamily, is one of the main biomarkers for vascular calcification. Aim. We aimed to evaluate the association between serum OPG levels and extent of coronary lesions in patients with acute myocardial infarction (MI). Methods. Consecutive patients hospitalized for an acute MI who underwent coronary angiography were included. SYNTAX score was calculated to assess the severity of coronary artery disease. The population was analysed in low (5 (3–6)), medium (11 (9–13)) and high (20 (18–23)) tertiles of SYNTAX score. Results. Among the 378 patients included, there was a gradual increa…

0139 : Extrahospital troponin measurement before admission for a ST segment elevation myocardial infarction

International audience; Background and aimEarly and reliable triage of patients is of major importance to promote rapid and appropriate treatments of patients with ST segment elevation myocardial infarction (STEMI). Extrahospital troponin measurement is used in primary care setting to help the identification of patients with suspected MI. From a regional survey (RICO), we aimed to investigate the frequence and hospital prognosis of STEMI patients with prehospital troponin (PT) measurement.Methods and resultsProspective study on 799 consecutive patients with STEMI included in RICO from March 2013 – 31 may 2015. Among the 799 patients, 38(5%) were identified with PT, from source files and pat…

Postnatal overfeeding in rats leads to moderate overweight and to cardiometabolic and oxidative alterations in adulthood.

In contrast to the masses of data on obesity, few data are available concerning the cardiometabolic and oxidative consequences of moderate overweight. The model of postnatal overfeeding (OF) induces an increase in body weight at weaning that remains during adult life. Litters of Wistar rats were either maintained at 12 pups (normal-fed group, NF), or reduced to 3 pups at birth in order to induce OF. At 6 months of age, metabolic parameters, circulating oxidative stress and aortic and coronary vasoreactivity were assessed. Cardiac susceptibility to ischemia-reperfusion injury was also evaluated ex vivo as were markers of cardiac remodeling. OF led to an increase in body weight at weaning (+5…

Downregulation and Nuclear Relocation of MLP During the Progression of Right Ventricular Hypertrophy Induced by Chronic Pressure Overload

Abstract The cardiac LIM domain protein MLP plays a crucial role in the architecture and mechanical function of cardiac myocytes. Mice lacking the MLP gene develop cardiac hypertrophy, dilated cardiopathy and heart failure. We investigated whether downregulation of MLP is induced by pressure overload and contributes to the physiopathology of cardiac hypertrophy and failure. We studied this mechanism in rat right ventricles submitted to pulmonary arterial hypertension, because it is known that this ventricle is very vulnerable to the deleterious effects of pressure overload. During the progression of cardiac hypertrophy to failure over a 31 days period there was a dramatic decrease by 50% of…

Identification and role of inflammatory oxygen free radicals in cardiac ischemia and reperfusion injury

Prolonged myocardial ischemia results in a variety of severe cellular, metabolic and ultra-structural damages. It is therefore generally accepted that reperfusion is an absolute prerequisite for the survival of ischemic tissue. However, reperfusion may precipitate arrhythmias, cause myocardial stunning and accelerate necrotic process. Oxygen free radicals have been suggested as possible mediators of reperfusioninduced injury and there is circumstantial evidence that supports this hypothesis. Indirect evidence in support of this concept derives from studies in which antioxidant enzymes, enzyme inhibitors, free radical scavengers and iron chelators are able to protect against reperfusion inju…

Telomere length and cardiovascular disease

SummaryTelomeres are structures composed of deoxyribonucleic acid repeats that protect the end of chromosomes, but shorten with each cell division. They have been the subject of many studies, particularly in the field of oncology, and more recently their role in the onset, development and prognosis of cardiovascular disease has generated considerable interest. It has already been shown that these structures may deteriorate at the beginning of the atherosclerotic process, in the onset and development of arterial hypertension or during myocardial infarction, in which their length may be a predictor of outcome. As telomere length by its nature is a marker of cell senescence, it is of particula…

Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes.

International audience; Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and …

0132 : Oxidative stress and cardio-metabolic alterations induced by postnatal programming can be reversed in adulthood by a short-term moderate caloric restriction

Postnatal overfeeding (PNOF) in rodents induces early programming of cardio-metabolic risk. Our aim was to determine if a moderate diet restriction could restore cardio-metabolic alterations induced by PNOF. Immediately after birth, litters of C57BL/6 mice were either maintained at 9 (normal litter, NL), or reduced to 3 (small litter, SL) to induce PNOF. At weaning, all mice received a standard diet ad libitum (AL). At 6 month of age, half of the NL and SL mice were assigned to a moderate 20% calorie restriction (CR: NLCR, SLCR) for one month, while the other mice continued to eat AL (AL: NLAL, SLAL). Glucose and insulin tolerance tests, cardiac function (echocardiography), body composition…

The Free Oxygen Radicals Test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction

International audience; Background and aim: Reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases including cardiovascular diseases. Several methods have been developed for the direct or indirect measurement of oxygen free radical and its by-products. The current study was designed to validate the new Free Oxygen Radicals Test (FORT) and to investigate the potential relationships between ROS and clinical or biological factors in male patients with acute myocardial infarction (AMI). Methods: We analysed FORT values in samples from 66 patients with AMI. Results: FORT values ranged from 324 to 1198 FORT units, with a median value of 581 (494-754) FORT units.…

Impact of high-fat diet on antioxidant status, vascular wall thickening and cardiac function in adult female LDLR&lt;sup&gt;–/–&lt;/sup&gt; mice

International audience; Background: Western diet, rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk. We thus investigated in female mice the influence of this diet on plasma antioxidant status, vascular wall thickening and cardiac function. Methods and Results: Adult female C57BL/6J wild type (WT) and LDLR–/– mice were fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks. HFD induced an increase in plasma lipids and vitamin C (Vit C) levels in both groups but at a much higher level in LDLR–/– and a decrease in plasma ascorbyl free radical levels to Vit C ratio (an endogenous oxidative stress index) in LDLR–/–. We only found a slight decr…

Ischemic stroke increases heart vulnerability to ischemia-reperfusion and alters myocardial cardioprotective pathways

Background and Purpose— For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury. Methods— Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue sta…

Brain-Heart interactions during ischemic processes: Clinical and experimental evidences

International audience

Growth Differentiation Factor-15 (GDF-15) Levels Are Associated with Cardiac and Renal Injury in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass

International audience; Objective: Growth differentiation factor-15 (GDF-15) has been identified as a strong marker of cardiovascular disease; however, no data are available concerning the role of GDF-15 in the occurrence of organ dysfunction during coronary artery bypass grafting (CABG) associated with cardiopulmonary bypass (CPB). Methods: Five arterial blood samples were taken sequentially in 34 patients from anesthesia induction (IND) until 24 h after arrival at the intensive care unit (ICU). Plasma levels of GDF-15, follistatin-like 1 (FLST1), myeloperoxidases (MPO), hydroperoxides and plasma antioxidant status (PAS) were measured at each time-point. Markers of cardiac (cardiac-troponi…

Acute Administration of Epirubicin Induces Myocardial Depression in Isolated Rat Heart and Production of Radical Species Evaluated by Electron Spin Resonance Spectroscopy

The aim of our study was to evaluate the acute effect of epirubicin (EPI), an anthracycline anticancer drug, on the evolution of cardiac functional parameters and production of reactive oxygen/nitrogen species (RONS). Isolated perfused rat hearts were subjected to 70 minutes of EPI (10.3 microM) infusion and to 5 minutes of isoproterenol (ISO, 0.1 microM) at the end of the protocol. Coronary flow (CF), left ventricular developed pressure (LVDP), and lactate dehydrogenase (LDH) release in the coronary effluents were evaluated throughout the protocol. RONS were detected in the coronary effluents by electron spin resonance spectroscopy with a spin probe, 1-hydroxy-3-carboxy-pyrrolidine (CP-H, …

Circulating leukocyte telomere length and oxidative stress: A new target for statin therapy

International audience; Objectives: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation.Methods and results: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without …

Mechanics Insights of Alpha-Lipoic Acid against Cardiovascular Diseases during COVID-19 Infection

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in late December 2019. Since then, COVID-19 has spread rapidly worldwide and was declared a global pandemic on 20 March 2020. Cardiovascular complications are rapidly emerging as a major peril in COVID-19 in addition to respiratory disease. The mechanisms underlying the excessive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities remain only partly understood. SARS-CoV-2 infection is caused by binding of the viral surface spike (S) protein to the human angiotensin-converting enzyme 2 (ACE2), followed by the activation of the S protein by transme…

Physiological and metabolic actions of mycophenolate mofetil on cultured newborn rat cardiomyocytes in normoxia and in simulated ischemia

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute rejection after heart transplantation. As with other immunosuppressive drugs, MMF therapy is associated with several adverse effects. However, the direct effects of MMF on myocardial tissue has not been yet evaluated. The aim of the work was thus to evaluate the effects of MMF on isolated cardiomyocytes (CM) in normal conditions and in an in vitro model of simulated ischemia (SI; substrate-free hypoxia) and reperfusion (R; reoxygenation). Myocyte-enriched cultures were prepared from newborn rat heart ventricles. The transmembrane potentials were recorded using conventional microelectrodes and the cell contracti…

Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats.

Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today&rsquo

The neuropeptide calcitonin gene-related peptide differently modulates proliferation and differentiation of smooth muscle cells in culture depending on the cell type

Abstract Calcitonin gene-related peptide (CGRP) is a neuropeptide present around vasculature very early during development, when smooth muscle cells (SMC) are still proliferating and not yet totally differentiated. We investigated the effects of CGRP on proliferation and differentiation of SMC in culture; 10 −7 M CGRP added in the medium of cultured smooth muscle cells every 2 days did not significantly changed cells growth rate in 1% FCS. At the opposite, this treatment modulated proliferation of cells grown in 10% FCS medium. Two distinct populations of SMC with different growth rates were obtained from our primary cultures. SMC which proliferated slowly in the presence of 10% fetal calf …

Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs).

Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or dama…

Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects

L-Arginine (L-Arg) is a conditionally essential amino acid in the human diet. The most common dietary sources of L-Arg are meat, poultry and fish. L-Arg is the precursor for the synthesis of nitric oxide (NO); a key signaling molecule via NO synthase (NOS). Endogenous NOS inhibitors such as asymmetric-dimethyl-L-Arg inhibit NO synthesis in vivo by competing with L-Arg at the active site of NOS. In addition, NOS possesses the ability to be "uncoupled" to produce superoxide anion instead of NO. Reduced NO bioavailability may play an essential role in cardiovascular pathologies and metabolic diseases. L-Arg deficiency syndromes in humans involve endothelial inflammation and immune dysfunctions…

Anti-hypertensive effects of Rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats

International audience; Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, RO…

Can aminothiols be distinguished from reactive oxygen species?

Glutathione is considered the major natural antioxidant, protecting cells from oxidative stress. Patel and colleagues used plasma levels of the aminothiols cystine and glutathione to quantify oxidative stress in patients with coronary artery disease, and show that the cystine/glutathione ratio is associated with increased mortality. Is this a new approach for clinical risk stratification?

General oxidative stress during doxorubicin-induced cardiotoxicity in rats: Absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid

International audience; To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) and O₂*⁻ (dihydroethidium fluorescence) content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX (+16%), but this was due to ascites. Histologic…

Comparative effects of equivalent intakes of 18:3 (n-3) and of marine (n-3) fatty acids on rat cardiac phospholipid contents and fatty acid compositions

Abstract Three groups of male Sprague-Dawley rats were fed for 4 weeks purified diets containing 15% by weight of oil mixtures varying in the nature and content of (n-3) polyunsaturated fatty acids (PUFA) but supplying similar levels of 18:2 (n-6) (10% of the total dietary fatty acids) and of saturated fatty acids (19% of the total fatty acids). The First diet (“Low 18:3”) contained small amounts of 18:3 (0.5% of the total fatty acids), the second (“18:3”) contained linolenic acid (10% of the total fatty acids) as the only source of (n-3) PUFA and the third one (“LC (n-3)”) contained the same amount of long chain (n-3) PUFA (mainly 20:5 and 22:6). Heart phospholipid classes were separated b…

Postnatal Overfeeding Causes Early Shifts in Gene Expression in the Heart and Long-Term Alterations in Cardiometabolic and Oxidative Parameters

International audience; Background: Postnatal overfeeding (OF) in rodents induces a permanent moderate increase in body weight in adulthood. However, the repercussions of postnatal OF on cardiac gene expression, cardiac metabolism and nitro-oxidative stress are less well known. Methodology/Principal Findings: Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal-fed group, NF), or reduced to 3 in order to induce OF. At weaning, mice of both groups received a standard diet. The cardiac gene expression profile was determined at weaning and cardiac metabolism and oxidative stress were assessed at 7 months. The cardiac expression of several genes, including membe…

The Yin and Yang of alarmin S100B in the protection of myocardium

0131 : Impact of overweight on anthracycline and trastuzumab-induced cardiotoxicity: experimental study in mice

Trastuzumab (TRZ), a humanized monoclonal antibody against Human Epidermal Growth Factor Receptor 2 (HER2) oncogene, is believed to potentiate doxorubicin (DOX) cardiotoxicity, resulting in left ventricular dysfunction. Few data indicate that overweight could influence DOX-induced cardiotoxicity, and no study has already evaluated the impact of moderate overweight on the cardiotoxic effect of DOX alone or in combination with TRZ. Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce programming of ~15% overweight through postnatal overfeeding. At 4 months, in order to evaluate the potentiation…

0053 : Short-term moderate diet restriction in adulthood can reverse alterations of cardiac function induced by postnatal overfeeding in mice

Postnatal overfeeding (OF) in rodents induces early programming of cardio-metabolic risk: permanent moderate increase in body weight, metabolic disorders and progressive alterations of cardiac function in adulthood. Our aim was to determine whether moderate diet restriction, performed at the time where these disorders are acquired, could restore cardiac function and ameliorate post-ischemic recovery.Immediately after birth, litters of C57BL/6 mice were either maintained at 9 (normal-fed group, NF), or reduced to 3 in order to induce OF. At weaning, mice of both groups received a standard diet ad libitum (AL). At 6 months of age, half of the NF mice and OF mice were assigned to a moderate 20…

Potential role of the neuropeptide CGRP in the induction of differentiation of rat hepatic portal vein wall.

The media of the rat hepatic portal vein is composed of an internal circular muscular layer (CL) and an external longitudinal muscular layer (LL). These two perpendicular layers differentiate progressively from mesenchymal cells within the first month after birth. In this paper, we studied the development of calcitonin gene-related peptide (CGRP) innervation during post-natal differentiation of the vessel. We show that CGRP innervation is already present around the vessel at birth in the future adventitia but far from the lumen of the vessel. Progressively, CGRP immunoreactive fibers reached first LL then CL. CL by itself become only innervated at day 14 after birth. This corresponds to the…

Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.

We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and …

0134 : Atrial fibrillation is associated with a marker of endothelial function and oxidative stress in patients with acute myocardial infarction

Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) e48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients wit…

The Activation Pattern of the Antioxidant Enzymes in the Right Ventricle of Rat in Response to Pressure Overload is of Heart Failure Type

In the left ventricle subjected to pressure overload activity, the antioxidant enzymes increased at the hyperfunctional stage. During the transition to heart failure, these enzymes are down-regulated, oxidative stress increases, and apoptosis progresses. Maladaptative activation of the antioxidant enzymes at an early stage may contribute to the intrinsic vulnerability of right ventricle to pressure overload. The authors studied changes in expression and activity of the enzymes manganese and copper-zinc superoxide dismutases, glutathione peroxidase, and catalase in the right ventricle of rat following induction of pulmonary hypertension by injection of monocrotaline. Increase in the manganes…

Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction

International audience; Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI.Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) !48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample.Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly o…

The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress, and Inflammation in Protective and Adaptive Responses

International audience; The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which medi…

Asymmetric dimethylarginine (ADMA) and hyperhomocysteinemia in patients with acute myocardial infarction

We sought to investigate the association between increased levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and total plasma homocysteinemia (tHcy) in patients with acute myocardial infarction (AMI).In 138 patients hospitalized for AMI24 h on admission, serum levels of ADMA, its symmetric stereoisomer (SDMA) and tHcy were measured.ADMA was positively associated with SDMA (p0.001) and tHcy (p=0.03) but not with estimated glomerular filtration rates (eGFR, p=0.96), while tHcy strongly correlated with eGFR (p=0.002) and SDMA (p0.001). By multiple linear regression, SDMA but not ADMA was independently associated with tHcy (p=0.005).Our findings sugges…

The Multifaceted Interplay between Atrial Fibrillation and Myocardial Infarction: A Review

International audience; This review was conducted to emphasize the complex interplay between atrial fibrillation (AF) and myocardial infraction (MI). In type 1 (T1) MI, AF is frequent and associated with excess mortality. Moreover, AF after hospital discharge for T1MI is not rare, suggesting the need to improve AF screening and to develop therapeutic strategies for AF recurrence. Additionally, AF is a common trigger for type 2 MI (T2MI), and recent data have shown that tachyarrhythmia or bradyarrhythmia could be a causal factor in, respectively, 13–47% or 2–7% of T2MI. In addition, AF is involved in T2MI pathogenesis as a result of severe anemia related to anticoagulants. AF is also an unde…

249 Validation of assessment of circulate oxidative stress markers by the Free Oxygen Radicals Testing (FORT) assay among patients with an acute myocardial infarction

BackgroundFree oxygen radicals play an important role in the pathogenesis of many diseases including cardiovascular diseases, diabetes, cancer and aging. Several methods were developed for the direct or indirect measurement of oxygen free radical and its by-products. Using a new Free Oxygen Radicals Testing (FORT) the current study is designed first to validate the device and to investigate the potential relationships between the ROS and clinical or biological factors in human serum from a population of men with an acute myocardial infarction (AMI).MethodsWe first determined the effect of storage, variability and reproducibility of the FORT test in serum. Then we used the test in 66 patient…

Iron overload does not potentiate doxorubicin induced cardiotoxicity in vivo in mice and in vitro in cardiomyocytes cell cultures

Background: Doxorubicin (DOX), an anticancer anthracycline, is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relations between iron metabolism and DOX-induced cardiotoxicity remain a matter of controversy. Methods: Firstly, we used an in vivo murine model of iron overloading (IO) where male C57BL/6 mice received during 3 weeks (D0-D20) a daily dextran-iron injection (15 mg/kg/day.) and then (D21) a single dose of 6 mg/kg DOX. We evaluated cardiac function with echocardiography, myocardial gene's expression, nitro-oxidative stress levels and iron status. Secondly, the anti-proliferative activity o…

Modulation by the n-6 to n-3 PUFA ratio of cardiac phospholipids of the anti-arrhythmic effects of lidocaine

Comunication orale : Demaison L.Comunication orale : Demaison L.; Background: Enrichment of cardiac phospholipids with eicosapentaenoic acid (EPA) is known to be cardioprotective during ischemia/reperfusion. This study aimed at studying the effect of dietary EPA-rich fish oil on the occurrence of severe reperfusion arrhythmias, at determining if the anti-arrhythmic lidocaine modulates that effect and at trying to evaluate the mechanism of these treatments. Materials and Methods: Rats were fed two diets differing in their PUFA composition for 8 weeks. The first one contained 10% of sunflower seed oil (SSO) and the second one 5% of fish oil (FO) plus 5% of SSO. The hearts were then perfused a…

013 Pre-infarction angina and cardiovascular complications in non ST segment elevation myocardial infarction: Data from the RICO survey

BackgroundThe presence of preinfarction angina (PIA) has been shown to confer cardioprotection after ST segment elevation myocardial infarction (MI). However, the impact of PIA in non ST segment elevation (NSTEMI) remains to be determined.Patients and MethodsFrom the obseRvatoire des Infarctus de Côte d’Or (RICO) survey, 1541 consecutive patients admitted in intensive care unit with a first NSTEMI were included in the study. Patients who experienced chest pain 1) and 30-day mortality were collected.ResultsAmong the 1541 patients included in the study, 693 patients presented PIA. Baseline clinical characteristics were similar for the 2 groups. There was no significant difference for the GRAC…

0126: New regulators of iron metabolism, Hepcidin and Erythroferrone, in acute myocardial infarction.

Background Dysfunctional iron storage and transport are common in patients with chronic heart failure and associated with poor prognosis. Body iron could contribute to the pathogenesis of coronary artery disease (CAD) through its ability to induce oxidative stress. However, studies on the relationship between iron metabolism and CAD have yielded conflicting results. Patients and Methods From the obseRvatoire des Infarctus de Cote d’Or (RICO) survey, 31 consecutive patients admitted in Intensive Care Unit for a first AMI were included. Serum concentrations of iron, transferrin, ferritin, the iron-regulatory hormone hepcidin and erythroferrone (a new hepcidin-regulating hormone), transferrin …

Diabetes, oxidative stress and therapeutic strategies.

Abstract Background Diabetes has emerged as a major threat to health worldwide. Scope of Review The exact mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of reactive oxygen species (ROS), largely due to hyperglycemia, causes oxidative stress in a variety of tissues. Oxidative stress results from either an increase in free radical production, or a decrease in endogenous antioxidant defenses, or both. ROS and reactive nitrogen species (RNS) are products of cellular metabolism and are well recognized for their dual role as both deleterious and beneficial species. In type 2 diabetic patients, oxidative stress is closely associated with ch…

Short-term atorvastatin treatment does not modify neointimal morphology but reduces MMP-2 expression in normocholesterolemic rabbit stented arteries.

The aim of our study was to explore some potential pleiotropic effects of atorvastatin, after stenting in the iliac arteries of normocholesterolemic rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized into either the control group (standard chow, CTRL, n = 15) or the atorvastatin group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were harvested for histomorphometry and neointimal analysis [macrophages, matrix metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular smooth muscle cells, and collagen]. Atorvastatin did not induce significant histomorphometric and inflammatory modifications but reduced neointimal expression …

A member of the TGF-β superfamily, GDF11: functions in the cardiac regeneration, perhaps an “elixir of youth?”

The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases

International audience; Among the numerous molecules that are being studied for their potential utility as biomarkers of cardiovascular diseases, much interest has been shown in the superfamily of tumor necrosis factor (TNF) receptors. Members of this family include osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). These signals may be expressed and regulated, and their functions could be involved in several physiological and pathological processes. The relationship between bone regulatory proteins and vascular biology has attracted attention, and it has been suggested that OPG may medi…

Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single su…

The iron-regulatory hormone hepcidin: A possible therapeutic target?

The maintenance of stable extracellular and intracellular iron concentrations requires the coordinated regulation of iron transport into plasma. Iron is a fundamental cofactor for several enzymes involved in oxidation-reduction reactions. The redox ability of iron can lead to the production of oxygen free radicals, which can damage various cellular components. Therefore, the appropriate regulation of systemic iron homeostasis is decisive in vital processes. Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. It is synthesized in hepatocytes and in other cells and released into the circulation. It inhibits the release of iron from enterocytes of the duodenum…

Comparison of the effects of valproate, ethosuximide, phenytoin, and pentobarbital on cerebral energy metabolism in the rat.

The acute effects of valproate (200 and 400 mg/kg), ethosuximide (200 and 400 mg/kg), phenytoin (25 and 50 mg/kg), and pentobarbital (30 and 60 mg/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral content of energy metabolites and by evaluating the rate of metabolite utilization following decapitation. The treatments did not affect the levels of phosphocreatine (PCr), ATP, ADP, and AMP, but did enhance the glycogen or glucose stores. Pentobarbital induced a decrease in lactate, whereas valproate led to a decrease in pyruvate and an increase in lactate. Calculation of the metabolite fluxes after decapitation showed that all treatments delayed the rate of ATP ut…

In vivo and in vitro antioxidant properties of furosemide

The aim of this study was to investigate in vivo and in vitro antioxidant properties of furosemide. In vitro, human red blood cells were submitted to oxidative stress (AAPH), in absence or in presence of different concentrations of furosemide. Potassium efflux was measured in order to quantify the oxidative stress after the action of AAPH on red blood cells. Allophycocyanin assay was also used to investigate antioxidant capacities of furosemide. For the in vivo experiment, male Wistar rats were used. A control group (n = 5) was treated by a daily intraperitoneal injection of saline solution (0.2 ml); 2 other groups (J0 and J+) were treated for 7 days by one daily intraperitoneal injection o…

Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of l-carnitine by d-carnitine and a γ-butyrobetaine hydroxylase inhibitor

Abstract This study was designed to examine whether the depletion of l -carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received d -carnitine for 2 days and 3-(2,2,2-trimethylhydrazinium)propionate (mildronate), a non-competitive inhibitor of γ-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to …

Increased oxidative stress is responsible for ether-lipid loss in the retina of senescence accelerated mouse (SAM)

International audience; Purpose: Ether–lipids represent an important class of retinal phospholipids but their exact functions are still unknown. They might act as antioxidants since the vinyl–ether double bond they contain could be the target for newly formed oxygenated radicals. In this work, we investigated the status of ether–lipids and aldehydes, their oxidative degradation products in the retina of a mouse model for aging, the senescence–accelerated mouse prone 8 (SAM P8), in which we reported a reduction of retinal function following 12 months of age (ARVO 2004 E–abstract 797). We completed this study by evaluating the oxidative stress in the retina. Methods: The quantification of eth…

Alpha-Lipoic Acid – an Antioxidant with Protective Actions on Cardiovascular Diseases

0135 : New regulators of iron metabolism, hepcidin and erythroferrone, in acute myocardial infarction

Background Dysfunctional iron storage and transport are common in patients with chronic heart failure and associated with poor prognosis. Body iron could contribute to the pathogenesis of coronary artery disease (CAD) through its ability to induce oxidative stress. However, studies on the relationship between iron metabolism and CAD have yielded conflicting results. Patients and methods from the obseRvatoire des Infarctus de Cote d’Or (RICO) survey, 31 consecutive patients admitted in Intensive Care Unit for a first AMI were included. Serum concentrations of iron, transferrin, ferritin, the iron-regulatory hormone hepcidin and erythroferrone (a new hepcidinregulating hormone), transferrin s…

Lidocaine inhibits potassium efflux and hemolysis in erythrocytes during oxidative stress in vitro.

Lidocaine is a widely used local anesthetic agent. The aim of this work was to study the action of lidocaine on human red blood cells exposed to an oxidative stress in vitro. Blood was obtained from healthy volunteers. After separation from plasma, the erythrocytes were suspended in phosphate buffer. Oxidative stress was induced by incubation with a free radical generator, the 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Erythrocytes were incubated with or without lidocaine at two concentrations (36.93 and 73.85 microM) and with or without AAPH (20 mM). Electron paramagnetic resonance (EPR) spectroscopy was performed to identify the free radical species generated by AAPH using the s…

0127: Atrial fibrillation is associated with a marker of endothelial function and oxidative stress in patients with acute myocardial infarction

Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients wit…

Neuroprotective Potential of GDF11: Myth or Reality?

In the brain, aging is accompanied by cellular and functional deficiencies that promote vulnerability to neurodegenerative disorders. In blood plasma from young and old animals, various factors such as growth differentiation factor 11 (GDF11), whose levels are elevated in young animals, have been identified. The blood concentrations of these factors appear to be inversely correlated with the age-related decline of neurogenesis. The identification of GDF11 as a “rejuvenating factor” opens up perspectives for the treatment of neurodegenerative diseases. As a pro-neurogenic and pro-angiogenic agent, GDF11 may constitute a basis for novel therapeutic strategies.

Effects of bupivacaine on human erythrocytes submitted to stress and evidence for an interaction between bupivacaine and flumazenil

Aims To examine the effects of bupivacaine on erythrocytes submitted to an oxidative stress (AAPH) and to provide evidence for an in vitro interaction between bupivacaine and flumazenil. Methods Human erythrocytes were studied with or without AAPH in the presence of different concentrations of bupivacaine (0.15, 0.3, 0.9 and 1.8 mmol l−1 ), or flumazenil (0.16 mmol l−1 ) and with the association of flumazenil and two doses of bupivacaine (0.15 and 0.3 mmol l−1 ). Potassium efflux was measured by flame photometry at t0, and every 30 min for 2 h. Results In the absence of AAPH, extracellular potassium remained unchanged. Oxidative stress induced a significant increase in extracellular potassi…

Iron, oxidative stress, and redox signaling in the cardiovascular system.

The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are invo…

Combining Sirolimus-eluting Stents and External Irradiation in Cholesterol-fed Rabbits Increased Incomplete Stent Apposition and Decreased Re-endothelialization

Restenosis after the implantation of a drug-eluting stent or after vascular irradiation therapy shares similar physiopathological mechanisms. No experimental data are currently available on vascular wall behavior after external irradiation on arteries stented with sirolimus-eluting stents (SES). Ten New Zealand white rabbits received a 0.5% cholesterol-enriched chow for 1 month. Bilateral iliac artery stent implantation was then performed with an SES (Cypher; Cordis Corp). The animals were randomized into either an irradiated group (I, 2 Gy external x-ray irradiation, n = 5) or a control group (C, n = 5). The cholesterol-enriched chow was continued for 1 additional month after stent implant…

High Serum Cholesteryl Ester Transfer Rates and Small High-Density Lipoproteins Are Associated With Young Age in Patients With Acute Myocardial Infarction

Objectives Our aim was to characterize cholesteryl ester transfer protein (CETP) activity in the early phase of acute myocardial infarction (MI). Background Cholesteryl ester transfer protein catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) donors to apolipoprotein B-containing lipoprotein acceptors. Methods The CETP concentration, lipid profiles, and the rate of cholesteryl ester transfer (CET) from a tracer dose of radiolabeled HDL toward endogenous lipoproteins were determined within 24 h after symptom onset. Results Among 347 patients with first MI, CETP concentration, triglycerides, and non–HDL-cholesterol increased across tertiles of the CET rate, where…

Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex.

Calcitonin gene-related peptide (CGRP) plays an important role in the mediation of protective effects observed in situations such as ischemic preconditioning in rat hearts. In this study, we investigated in H9c2 rat cardiomyoblasts if the protective effect of CGRP could be linked to an inhibitory effect on the apoptotic pathway. We also determined the specificity of observed effects by treatment with adrenomedullin (ADM) in stress conditions generated by 100 microM hydrogen peroxide. Using MTT assays, we demonstrate that a pretreatment with CGRP decreases by half the loss of cell viability induced by H(2)O(2). CGRP inhibits phosphatidylserine externalization, caspase 3 activation and DNA fr…

Short-term moderate diet restriction in adulthood can reverse oxidative, cardiovascular and metabolic alterations induced by postnatal overfeeding in mice

AbstractWe aimed to determine whether moderate diet restriction could restore cardiac, oxidative and metabolic alterations induced by postnatal overfeeding (PNOF). Litters of C57BL/6 male mice were either maintained at 9 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce PNOF. At 6 months, half of the NL and SL mice were subjected to 20% calorie-restriction (CR: NLCR, SLCR) for one month, while the other half continued to eat ad libitum (AL: NLAL, SLAL). Six-month old SL mice presented overweight, fat accumulation, hyperleptinemia, glucose intolerance, insulin resistance, increased cardiac ROS production and decreased left ventricular ejection fraction (LVEF). After …

0004 : Overweight in mice induced by perinatal programming exacerbates doxorubicin and trastuzumab cardiotoxicity

Background Trastuzumab (TRZ) is believed to potentiate doxorubicin (DOX) cardiotoxicity, resulting in left ventricular dysfunction. There is some evidence that overweight could influence anticancer drug-induced cardio \toxicity, though no study has evaluated the impact of moderate overweight, induced by postnatal nutritional programming, on the cardiotoxic effects of DOX alone or in combination with TRZ. Methods Immediately after birth, litters of C57BL/6 mice were either maintained at 9 pups (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce programming of ~15% overweight through postnatal overfeeding. At 4 months, NL and SL mice received a single intraperitoneal in…

0229: Alterations of cardiac function induced by postnatal overfeeding can be reversed by moderate diet restriction

Postnatal overfeeding (OF) in rodents induces a permanent moderate increase in body weight, metabolic disorders and progressive alterations of cardiac function. Our aim was to determine whether moderate diet restriction could restore cardiac function in mature overfed mice. Immediately after birth, litters of C57BL/6 mice were either maintained at nine (normal-fed group, NF), or reduced to three in order to induce OF. At weaning, mice of both groups received a standard diet ad libitum (AL). At 6 months of age, half of the OF mice were assigned to a moderate 20% calorie restriction (CR, OF-CR) for one month, while NF and the other half of the OF mice continued to eat ad libitum (NF-AL, OF-AL…

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly…

Increased Symmetric Dimethylarginine Level Is Associated with Worse Hospital Outcomes through Altered Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction

International audience; Objectives: We aimed to investigate whether SDMA-symmetric dimethylarginine-the symmetrical stereoisomer of ADMA-might be a marker of left ventricular function in AMI.Background: Asymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF).Methods: Cross sectional prospective study from 487 consecutive patients hospitalized 2, and death.Results: Patients were analysed based on SDMA tertiles. Sex, diabetes, dyslipidemia, and prior MI were similar for all tertiles. In contrast, age and hypertension increased across the tertiles (p<0.001). From the first to the last tertile, GRACE risk score was e…

Apoptosis induced in vascular smooth muscle cells by oxidative stress is partly prevented by pretreatment with CGRP.

Creatine kinase is the main target of reactive oxygen species in cardiac myofibrils.

Abstract Reactive oxygen species (ROS) have been reported to alter cardiac myofibrillar function as well as myofibrillar enzymes such as myosin ATPase and creatine kinase (CK). To understand their precise mode and site of action in myofibrils, the effects of the xanthine/xanthine oxidase (X/XO) system or of hydrogen peroxide (H 2 O 2 ) have been studied in the presence and in the absence of phosphocreatine (PCr) in Triton X-100–treated cardiac fibers. We found that xanthine oxidase (XO), with or without xanthine, induced a decrease in maximal Ca 2+ -activated tension. We attributed this effect to the high contaminating proteolytic activity in commercial XO preparations, since it could be p…

Pre-Infarction Angina and Outcomes in Non-ST-Segment Elevation Myocardial Infarction: Data from the RICO Survey

BACKGROUND: The presence of pre-infarction angina (PIA) has been shown to confer cardioprotection after ST-segment elevation myocardial infarction (STEMI). However, the clinical impact of PIA in non-ST-segment elevation myocardial infarction (NSTEMI) remains to be determined. METHODS AND RESULTS: From the obseRvatoire des Infarctus de Côte d'Or (RICO) survey, 1541 consecutive patients admitted in intensive care unit with a first NSTEMI were included. Patients who experienced chest pain <7 days before the episode leading to admission were defined as having PIA and were compared with patients without PIA. Incidence of in-hospital ventricular arrhythmias (VAs), heart failure and 30-day mortali…

Humanin: A mitochondria-derived peptide with emerging properties.

Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential.

International audience; Diabetes has emerged as a major threat to worldwide health. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that the excess generation of reactive oxygen species (ROS) associated with hyperglycemia, causes oxidative stress in a variety of tissues. In this context, various natural compounds with pleiotropic actions like lipoic acid (LA) are of interest, especially in metabolic diseases such as diabetes. LA, either as a dietary supplement or a therapeutic agent, modulates redox potential because of its ability to match the redox status between different subcellular compartments as well as extracellularly. Both the oxidized (d…

Hypoxie et régénération cardiaque : une nouvelle approche paradoxale de la cardioprotection

IF 2.331; International audience

Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease.

International audience; OBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. METHODS: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratif…

C023 Evaluation de l’effet protecteur de l’acide dihydro-lipoïque vis-à-vis d’une séquence d’ischémie-reperfusion sur coeur isolé perfusé de rat et d’un stress oxydant induit in vitro sur le globule rouge

L’acide alpha-lipoique (AL) est un dithiol endogene aux proprietes antioxydantes. Au niveau intracellulaire, l’AL subit une reduction pour former l’acide dihydro-lipoique (DHLA) qui represente son metabolite le plus actif. L’objectif de ce travail a ete de preciser les effets d’un traitement in vitro par le DHLA sur 1) des coeurs isoles perfuses de rats soumis a une sequence d’ischemie-reperfusion (IR) et 2) des globules rouges (GR) soumis a une agression radicalaire. Les coeurs ont ete isoles, perfuses en mode Langendorff et soumis a une ischemie globale totale de 30 min suivie d’une reperfusion de 30 min. Cinq minutes avant l’ischemie et pendant toute la periode de reperfusion, il a ete a…

Characterization of Purified Green Bell Pepper Hydroperoxide Lyase Expressed by Yarrowia Lipolytica: Radicals Detection during Catalysis

International audience; The optimization of the expression of recombinant 6-His-tagged HPO lyase in Yarrowia lipolytica is described: 1800U/L of culture was detected at 24h of culture on a medium containing olive oil as the sole carbon source. The enzyme was purified by IMAC and showed an optimal pH at 5.5, an optimal temperature at 20^\circC and a Km value of 9μM with 13-HPOD substrate. The participation of radicals during the catalysis of purified bell pepper fruit hydroperoxide lyase has been observed by electron paramagnetic resonance spectroscopy and the yet unidentified radical species might be an alkyl or alkoxyl radical linked to the enzyme.

High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction

International audience; Objectives: Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA. Approach and Results: Blood samples from 612 consecutive patients hospitalized for acute MI ,24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethyl…

Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK.

Abstract Oxidative stress induced by a glucose/glucose oxidase (G/GO) generator system dose-dependently decreased the viability of cultured vascular smooth muscle cells (VSMC) as estimated by MTT assay. Cell death was induced in 40% of cells exposed to 0.2 IU/ml of the free radical generating mixture. Annexin-V labeling, Hoechst staining together with DNA laddering demonstrated that apoptosis was responsible for this cell loss. Pretreatment of the cells with 10−8 M calcitonin gene-related peptide (CGRP) significantly attenuated the damaging effect of the oxidative stress. Indeed, cell viability was estimated to be 80% in CGRP-treated group, instead of 60% in absence of CGRP treatment. This …

Skin Immunomodulation during Regeneration: Emerging New Targets

Adipose-Derived Stem Cells (ADSC) are present within the hypodermis and are also expected to play a pivotal role in wound healing, immunomodulation, and rejuvenation activities. They orchestrate, through their exosome, the mechanisms associated to cell differentiation, proliferation, and cell migration by upregulating genes implicated in different functions including skin barrier, immunomodulation, cell proliferation, and epidermal regeneration. ADSCs directly interact with their microenvironment and specifically the immune cells, including macrophages and T and B cells, resulting in differential inflammatory and anti-inflammatory mechanisms impacting, in return, ADSCs microenvironment and …

“Pro-youthful” factors in the “labyrinth” of cardiac rejuvenation

IF 3.350; International audience; The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro-pathways is essential to discover new approaches to regenerative therapies. (C) 2016 Elsevier Inc. All rights reserved.

Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: A model related to metabolic syndrome

Asymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats.90 male Sprague-Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our …