- Cardiomyopathy and Myosin Studies
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Muscle Physiology and Disorders
- Ion Channels and Receptors
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Viral Infections and Immunology Research
- Protein Kinase Regulation and GTPase Signaling
- Drug Transport and Resistance Mechanisms
- Ion Transport and Channel Regulation
- Protein Tyrosine Phosphatases
- Phosphodiesterase function and regulation
- Pulmonary Hypertension Research and Treatments
- Muscle metabolism and nutrition
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- Calpain Protease Function and Regulation
- Protease and Inhibitor Mechanisms
- Receptor Mechanisms and Signaling
Fondation pour l’innovation en Cadiométabolisme et Nutrition
2012-2019
Inserm
2007-2019
Sorbonne Université
2009-2019
Unité de recherche sur les maladies cardiovasculaires et métaboliques
2010-2019
Pitié-Salpêtrière Hospital
1989-2017
Assistance Publique – Hôpitaux de Paris
2015
Université Paris Cité
1989-2015
Icahn School of Medicine at Mount Sinai
2010-2013
Leiden University Medical Center
2012
Sanjay Gandhi Post Graduate Institute of Medical Sciences
2012
The cardiac ventricular myosin phenotype is developmentally and hormonally regulated.The genes coding for the two heavy chains (MHCs), a @, have been recently isolated characterized.In this study, we establish precise temporal expression of these MHC in correlation with both during development response to different thyroid hormone levels also document their other muscle tissues.The close observed between relative abundance a-and &MHC mRNAs corresponding isozymes demonstrates that produced by...
A decrease in the myocardial level of mRNA encoding Ca2(+)-ATPase sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs human end-stage heart failure, we compared SR levels left (LV) right ventricular (RV) specimens from 13 patients undergoing transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with infarctions; 3 diverse etiologies) control samples using rat cDNA probe....
Expression of the cardiac myosin isozymes is regulated during development, by hormonal stimuli and hemodynamic load. In this study, levels expression two isoforms (alpha beta) heavy chain (MHC) hypertrophy were investigated at messenger RNA (mRNA) protein levels. normal control sham-operated rats, alpha-MHC mRNA predominated in ventricular myocardium. response to aortic coarctation, there was a rapid induction beta-MHC followed appearance comparable parallel an increase left weight....
We studied the effect of chronic mechanical overloading on isoenzyme composition rat cardiac myosin in several experimental models: aortic stenosis (AS), incompetence (AI), aortocaval fistula (ACF), overload non-infarcted area after left coronary ligation (INF), and spontaneously hypertensive rats (SHR). Samples right ventricles were isolated from these hearts, myosins analyzed by electrophoresis non-dissociating conditions. The isoenzymes called V1, V2, V3 order decreasing mobility,...
The reduction in Ca2+ concentration during diastole and relaxation occurs differently normal hearts hypertrophied secondary to pressure overload. We have studied some possible molecular mechanisms underlying these differences by examining the function of sarcoplasmic reticulum expression gene encoding its Ca2(+)-ATPase rat with mild severe compensatory hypertrophy induced abdominal aortic constriction. Twelve sham-operated rats 31 operated were 1 month after surgery. Eighteen animals...
Little is known concerning the molecular mechanisms responsible for changes in sarcoplasmic reticulum (SR) function during ontogenic development and aging except that amount of SR Ca(2+)-ATPase mRNA varies these conditions. The aim present work was to determine whether maturation requires expression specific isoforms synchronous accumulation mRNAs encoding proteins located SR. Thus, we have studied calsequestrin genes rat at different developmental stages from 14 fetal days 24 months age....
cAMP is one of the most important second messenger in heart. The discovery Epac as a guanine exchange factor (GEF), which directly activated by cAMP, raises question role this protein cardiac cells. Here we show that activation leads to morphological changes and induces expression hypertrophic markers. This process associated with Ca2+-dependent small GTPase, Rac. In addition, found activates prohypertrophic signaling pathway, involves Ca2+ sensitive phosphatase, calcineurin, its primary...
Cardiomyocytes use Ca2+ not only in excitation-contraction coupling but also as a signaling molecule promoting, for example, cardiac hypertrophy. It is largely unclear how triggers cardiomyocytes the presence of rapid and large fluctuations that occur during coupling. A potential route store-operated entry, drug-inducible mechanism requires stromal interaction 1 (STIM1). Store-operated entry can be induced cardiomyocytes, which prompted us to study STIM1-dependent with respect hypertrophy...
The development of cardiac hypertrophy secondary to pressure overload is accompanied by isoformic changes contractile proteins such as myosin and actin. 35S-Labeled complementary RNA (cRNA) probes in situ hybridization procedures were used for analysis the regional distribution newly formed transcripts from alpha-skeletal actin (alpha-sk-actin) beta-myosin heavy chain (beta-MHC) genes during early stages overload. study was performed 25-day-old rats submitted a thoracic aortic stenosis...
Aging is the main risk factor for cardiovascular diseases, but associated molecular mechanisms are poorly understood. The Wnt signaling pathway was shown to be induced during aging in muscle and skin, regulation role of aged vessel have not yet been addressed. While screening age-related changes gene expression intima/media human mammary arteries, we observed that frizzled 4 (Fzd4), a receptor, several targets Wnt/β-catenin/TCF [Wnt-inducible secreted protein 1 (WISP1), versican, osteopontin...
The second messengers cAMP and cGMP can be degraded by specific members of the phosphodiesterase superfamily or active efflux transporters, namely multidrug resistance-associated proteins (MRPs) MRP4 MRP5. To determine role MRP5 in cell signaling, we studied arterial SMCs, which effects cyclic nucleotide levels on SMC proliferation have been well established. We found that MRP4, but not MRP5, was upregulated during isolated human coronary artery SMCs following injury rat carotid arteries...
Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion infracted heart has been an important objective strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at cellular level, disturbance in Ca 2+ and redox homeostasis. In this study, we sought determine how acute inflammatory response contributes injury homeostasis after ischemia. Using a rat...
Multidrug resistance-associated protein 4 (MRP4, also known as Abcc4) regulates intracellular levels of cAMP and cGMP in arterial SMCs. Here, we report our studies the role MRP4 development progression pulmonary hypertension (PAH), a severe vascular disease characterized by chronically elevated artery pressure accompanied remodeling small arteries prelude to right heart failure premature death. expression was increased from patients with idiopathic PAH well WT mice exposed hypoxic...
Sarcoplasmic reticulum Ca 2+ ‐ATPase cDNA clones have been isolated from an adult rat heart library and the nucleotide sequence of mRNA determined. The has open reading frame 997 codons. It is identical to a stomach 90% isologous rabbit human slow/ cardiac cDNAs. Nuclease S 1 mapping analysis indicates that this corresponds main present in slow skeletal muscle it expressed various proportions smooth non‐muscle tissues, together with another isoform which differs form its 3′‐end.
Proliferation of vascular smooth muscle cells (VSMC) is a primary cause disorders and associated with major alterations in Ca2+ handling supported by loss the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine importance SERCA2a neointima formation, we have prevented its expression adenoviral gene transfer model balloon injury rat carotid artery. Two weeks after injury, intima/media ratio was significantly lower SERCA2a-infected than injured noninfected or...
Rat cardiac ventricular myosins were obtained from fetuses, young normal animals, and hypophysectomized adults.The purified proteins compared by several techniques: (i) electrophoresis in nondenaturing conditions (pyrophosphate buffer), (ii) oneand two-dimensional analysis after proteolytic cleavage, (iii) immunological blotting electrophoretic purification, (iv) competitive enzyme-linked immunosorbent assay.Antibodies specific to each of the two major isoenzymes adult rat heart (V1 V3...