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 …

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…

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

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…

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

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…

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

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…

Stress induced premature liver senecence in adulthood after transient postnatal overfeeding in mice

IF 2.043; International audience

0058 : Low circulating levels of Growth Differentiation Factor 15 (GDF-15) before coronary artery bypass surgery may predict post-operative atrial fibrillation

BackgroundPost-operative atrial fibrillation (POAF) following cardiac surgery has a high prevalence and is associated with considerable morbidity.AimsTo assess the role of GDF-15, a member of the TGFβsuperfamily, as a potential new predictor of POAF after off-pump (OFP) and on-pump (ONP) coronary artery bypass graft (CABG) surgery.MethodsThis observational study recruited the first 50 patients planned for OFP surgery and the first 50 patients planned for ONP surgery. Patients referred for CABG with the following exclusion criteria: age 80 years, previous atrial fibrillation/flutter, previous treatment with Amiodarone, previous cardiac surgery, emergency surgery. Included patients were equip…

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 …

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…

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…

Dépistage séquentiel de la FA silencieuse post-AVC (Stepwise screening for silent Atrial Fibrillation After Stroke : SAFAS study)

Introduction Un tiers des AVC cryptogeniques seraient secondaires a une fibrillation atriale (FA) silencieuse non-detectee par les methodes usuelles. Trois versants seraient impliques dans le developpement d’une arythmie (le substrat atrial, le modulateur, le declencheur). Objectifs L’objectif etait d’identifier les deregulations physiopathologiques conduisant au developpement de la FA. Patients et methodes Etaient inclus les patients hospitalises pour un AVC ischemique au sein de l’USINV du CHU de Dijon, d’etiologie indeterminee a la prise en charge. Le depistage de la FA combinait de maniere sequentielle la telemetrie, le Holter ECG prolonge et le Holter sous cutane. Les donnees cliniques…

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<sup>–/–</sup> 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…

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…

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…

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…

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…

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 …

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…

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…

0057 : Preoperative Growth Differentiation Factor 15 (GDF15) as a novel biomarker of acute kidney injury after cardiac bypass surgery

ObjectivePreviously, we demonstrated that preoperative plasma GDF15 levels significantly improved the prognostic value of the EuroSCORE for mortality after cardiac surgery. Despite the strong correlation between GDF15 and renal function, no data are available regarding the potential interest of preoperative GDF15 levels to improve the prediction of acute kidney injury (AKI) after coronary artery bypass grafting (CABG).Design134 patients operated on for CABG of whom 50 underwent offpump surgery at our university hospital were included in this prospective, observational study. Exclusion criteria were age 80 years, previous atrial fibrillation/flutter, previous severe renal failure (estimated …

Intérêt du growth differentiation factor 15 (GDF15) comme biomarqueur pronostique après la survenue d'un Accident Vasculaire Cérébral ischémique (AVC)

Introduction Le GDF15 est un biomarqueur de mauvais pronostic dans certaines pathologies cardiovasculaires comme le syndrome coronarien aigu. Son interet dans le domaine de AVC n’a ete que peu etudie a ce jour. Objectifs Notre travail consistait a l’evaluation des taux de GDF15 chez des patients hospitalises a la phase aigue d’un AVC ischemique traites par fibrinolyse et/ou thrombectomie. L’objectif principal etait d’evaluer l’association entre les taux de GDF15 et la recuperation fonctionnelle a 3 mois. Methodes Au total, 174 patients ont ete inclus entre le 16/01 et le 30/09/2017. Le consentement etait recueilli oralement. Des prelevements biologiques ont ete realises a l’admission du pat…

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…

Transient postnatal over nutrition induces long-term alterations in cardiac NLRP3-inflammasome pathway.

International audience; Background and aims: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice. Methods and results: Based on a model of mice exposed to PNOF through litter size reduction, we …

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…

Dietary superoxide dismutase protects against light-induced retinal oxidative stress in young senescence accelerated mice (SAM)

International audience

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…

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.

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 …