0000000000123211
AUTHOR
Jean-claude Guilland
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…
Docosahexaenoic acid, but not eicosapentaenoic acid, lowers ambulatory blood pressure and shortens interval QT in spontaneously hypertensive rats in vivo
International audience; This study was designed to evaluate the effects of individual dietary long-chain n-3 polyunsaturated fatty acids (LCPUFA) on hypertension and cardiac consecutive disorders in spontaneously hypertensive rats (SHR) as compared to Wistar-Kyoto rats (WKY). Rats were fed for 2 months an eicosapentaenoic (EPA)- or docosahexaenoic acid (DHA)-rich diet (240 mg/day) or an n-3 PUFA-free diet. Male SHR (n=6), implanted with cardiovascular telemetry devices, were housed in individual cages for continuous measurements of cardiovascular parameters (blood pressure (BP) and heart rate (HR)) during either activity or rest periods, ECG were recorded during the quiet period. The n-6 PU…
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…
Association between serum concentration of vitamin D and 1-year mortality in stroke patients.
<b><i>Background:</i></b> The prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency is high in patients presenting with an acute stroke, and it may be associated with greater clinical severity and a poor early functional prognosis. However, no data about its impact on long-term prognosis is available. In this study, we aimed to assess the association between 25(OH)D levels and 1-year mortality in stroke patients. <b><i>Methods:</i></b> From February to December 2010, 382 Caucasian stroke patients admitted to the Department of Neurology of the University Hospital of Dijon, France, were enrolled prospectively. Demographics and clinical informat…
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…
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…
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…
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…
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…
Effets d'une supplémentation en antioxydants sur les taux circulants des immunoglobulines IgA, IgG et IgM chez des femmes récemment mastectomisées, en traitement chimiothérapeutique
Resume Les methodes de traitement du cancer sont nombreuses et le plus souvent ont des effets secondaires importants ; c'est ainsi que la chimiotherapie a des effets deleteres sur le systeme immunitaire, en partie medies par le stress oxydatif. Ce travail evalue les benefices d'une supplementation avec des nutriments antioxydants chez 20 femmes de 30 a 60 ans, atteintes d'un cancer du sein, recemment mastectomisees et devant etre traitees par chimiotherapie. Les femmes ont ete distribuees en deux groupes ( n = 10) et recurent quotidiennement du β-carotene (15 mg), de la vitamine E avec du selenium (400 mg d'alphatocopherol et 50 μg de selenium) et de la vitamine C (2 g), pendant sept jours…
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…
Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations
Background: Methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism is heterogeneously distributed worldwide, with the highest and lowest frequencies of the T allele in Mexico and Africa, respectively, and a south-to-north gradient in Europe. Distribution of MTHFR 1298A→C is less well known. It has been hypothesized that 677T frequency could result in part from gene-nutrient interactions. Objective: The objective was to compare the association of 677T and 1298C alleles with plasma concentrations of homocysteine, folate, and vitamin B-12 in geographical areas with contrasting 677T allele frequencies. Design: Healthy young adults (n = 1:277) were recruited in Mexico City, the West Afr…
Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats
Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density …
MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled trial.
Aims To study how MTHFR 677C→T genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations. Methods 2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 μg of 5-methyl-THF, 3 mg of vitamin B6 and 20 μg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR …
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…
Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients
Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone…
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…
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 …