A5059464647- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Nuclear Structure and Function
- RNA Research and Splicing
- Ion Transport and Channel Regulation
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Cardiac Arrest and Resuscitation
- Click Chemistry and Applications
- Diet and metabolism studies
- Nitric Oxide and Endothelin Effects
- Estrogen and related hormone effects
- Signaling Pathways in Disease
- Sepsis Diagnosis and Treatment
- Metabolomics and Mass Spectrometry Studies
- Acute Myocardial Infarction Research
- Pharmacological Receptor Mechanisms and Effects
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- Vitamin C and Antioxidants Research
- Antimicrobial Peptides and Activities
- Muscle Physiology and Disorders
- Endoplasmic Reticulum Stress and Disease
Columbia University
2014-2024
Université Paris Cité
2021
Inserm
2021
Hôpital Européen Georges-Pompidou
2021
Paris Cardiovascular Research Center
2021
Albany Medical Center Hospital
2004-2020
Lerøy (Norway)
2019
New York Proton Center
2014
Royal College of Physicians
2014
Hamilton College
2007
Cardiomyopathy frequently complicates sepsis and is associated with increased mortality. Increased cardiac oxidative stress mitochondrial dysfunction have been observed during sepsis, but the mechanisms responsible for these abnormalities not determined. We hypothesized that NADPH oxidase 2 (NOX2) activation could be sepsis-induced cardiomyopathy. Treatment of isolated adult mouse cardiomyocytes low concentrations endotoxin lipopolysaccharide (LPS) total cellular reactive oxygen species...
Obesity and high saturated fat intake increase the risk of heart failure arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels could mitochondrial reactive oxygen species (ROS) in cardiomyocytes, leading to abnormalities calcium homeostasis function. investigated effect on function isolated ventricular myocytes. fatty acid palmitate causes a decrease respiration cardiomyocytes. Palmitate, but not monounsaturated oleate, an both total cellular...
Cardiomyopathy caused by lamin A/C gene mutations ( LMNA cardiomyopathy) is characterized increased myocardial fibrosis, which impairs left ventricular relaxation and predisposes to heart failure, cardiac conduction abnormalities. While we previously discovered abnormally elevated extracellular signal-regulated kinase 1/2 (ERK1/2) activities in cardiomyopathy, its role on the development of fibrosis remains unclear. We now showed that transforming growth factor (TGF)-β/Smad signaling...
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role the hypoxia-induced [Ca2+]i PASMCs and attendant HPV. In this study, we intended determine molecular mechanisms for hypoxic contractile responses PASMCs. Our data reveal occurs arteries, but not mesenteric arteries. Hypoxia caused large PASMCs, which diminished...
Background: Obesity and diets high in saturated fat increase the risk of arrhythmias sudden cardiac death. However, molecular mechanisms are not well understood. We hypothesized that an dietary could lead to abnormalities calcium homeostasis heart rhythm by a NOX2 (NADPH oxidase 2)-dependent mechanism. Methods: investigated this hypothesis feeding mice high-fat diets. In vivo telemetry, optical mapping, isolated myocyte imaging were used quantify arrhythmias, repolarization, transients,...
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An increase in intracellular calcium concentration ([Ca 2+ ] i ) pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses the lungs; however, underlying molecular mechanisms remain incompletely understood. We report, for first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity mouse resistance arteries (PAs), but not mesenteric arteries. Western blot analysis and immunofluorescence staining reveal expression of PLC-γ1 protein PAs PASMCs,...
Sepsis-induced cardiomyopathy (SIC) is associated with increased patient mortality. At present, there are no specific therapies for SIC. Previous studies have reported reactive oxygen species (ROS) and mitochondrial dysfunction during However, a unifying mechanism remains to be defined. We hypothesized that PKCδ required abnormal calcium handling cardiac sepsis genetic deletion of would protective. Polymicrobial induced by cecal ligation puncture (CLP) surgery decreased the ejection fraction...
Abstract Obesity and diabetes increase the risk of arrhythmia sudden cardiac death. However, molecular mechanisms caused by metabolic abnormalities are not well understood. We hypothesized that mitochondrial dysfunction high fat diet (HFD) promotes ventricular arrhythmia. Based on our previous work showing saturated causes calcium handling in cardiomyocytes, we uptake contributes to HFD-induced arrhythmic events. For experiments, used mice with conditional cardiac-specific deletion uniporter...
Breast cancer is the most common among women, and tamoxifen preferred drug for estrogen receptor-positive breast treatment. Many of these cancers are intrinsically resistant to or acquire resistance during Consequently, there an ongoing need drugs that have different molecular targets. Previous work has shown 8-mer cyclic 9-mer peptides inhibit in mouse rat models, interacting with unsolved receptor, while smaller than eight amino acids did not. We show use replica exchange dynamics predicts...
We previously showed that striated muscle-selective depletion of lamina-associated polypeptide 1 (LAP1), an integral inner nuclear membrane protein, leads to profound muscular dystrophy with premature death in mice. As LAP1 is also depleted hearts these mice, we examined their cardiac phenotype. Striated knockout mice display ventricular systolic dysfunction abnormal induction genes encoding cardiomyopathy related proteins. To eliminate possible confounding effects due skeletal muscle...
Abstract: A synthetic peptide that inhibits the growth of estrogen receptor positive (ER+) human breast cancers, growing as xenografts in mice, has been reported. The cyclic 9‐mer peptide, cyclo [EMTOVNOGQ], is derived from α ‐fetoprotein (AFP), a safe, naturally occurring protein produced during pregnancy, which itself anti‐estrogenic and anti‐breast cancer activity. To determine pharmacophore series analogs was prepared using solid‐phase synthesis. Analogs were screened 1‐day bioassay,...
Abstract Cyclo [EKTOVNOGN] (AFPep), a cyclic 9‐amino acid peptide derived from the active site of alpha‐fetoprotein, has been shown to prevent carcinogen‐induced mammary cancer in rats and inhibit growth ER + human breast xenografts mice. Recently, studies using replica exchange molecular dynamics predicted that TOVN region AFPep might form dynamically stable putative Type I beta‐turn, thus be biologically without additional amino acids. The presented this paper were performed determine...
Background: Conflicting data exist regarding the benefit of urgent coronary angiogram and percutaneous intervention (PCI) after sudden cardiac arrest, particularly in absence ST-segment elevation. We hypothesized that type lesions treated (stable versus unstable) influences derived from PCI. Methods: Data were taken between May 2011 2014 a prospective registry enrolling all arrest Paris suburbs (6.7 million inhabitants). Patients undergoing emergent included. Decision to perform PCI was left...
Mutations in LMNA encoding lamin A/C and EMD emerin cause cardiomyopathy muscular dystrophy. Lmna null mice develop these disorders have a lifespan of 7-8 weeks. Emd show no overt pathology normal skeletal muscle but with regeneration defects. We generated germline deletions both to determine the effects combined loss encoded proteins. Mice without are born at expected Mendelian ratio, grossly birth shorter lifespans than those lacking only A/C. However, there major differences between...
The response of vital organs to different types nutrition or diet is a fundamental question in physiology. We examined the cardiac 4 weeks high-fat mice, measuring metabolites and mRNA. Metabolomics showed dramatic differences after diet, including increases several acyl-carnitine species. RNA-seq data changes consistent with adaptations use more fatty acid as substrate an increase antioxidant protein catalase. Changes mRNA were correlated level for highly responsive genes. also found...