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Hypertrophic cardiomyopathy (HCM), a relatively common disease, is diagnosed clinically by unexplained cardiac hypertrophy and pathologically by myocyte hypertrophy, disarray, and interstitial fibrosis. HCM is the most common cause of sudden cardiac death (SCD) in the young and a major cause of morbidity and mortality in elderly. Hypertrophy and fibrosis(More)
During the past decade, more than 100 mutations in 11 causal gene coding for sarcomeric proteins, the gamma subunit of AMP-activated protein kinase and triplet-repeat syndromes and in mitochondrial DNA, have been identified in patients with hypertrophic cardiomyopathy (HCM). Genotype-phenotype correlation studies show significant variability in the(More)
Coronary artery disease (CAD) is a complex trait caused by a number of genetic and environmental factors. Recently, paraoxonase/arylesterase (PONA) enzyme has been implicated in the pathogenesis of atherosclerosis. There is a 10-40-fold variability in the activity of this enzyme among individuals. This variability is due to the presence of an A/G(More)
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetic disease caused by mutations in desmosomal proteins. The phenotypic hallmark of ARVC is fibroadipocytic replacement of cardiac myocytes, which is a unique phenotype with a yet-to-be-defined molecular mechanism. We established atrial myocyte cell lines expressing siRNA against(More)
M yheart is a cardiac-specific long-noncoding (lnc) RNA with targeted modulation of chromatin-modifying switching–defective/sucrose–nonfermenting complex via direct interaction with Brg1. Genetic induction of Myheart in mouse heart has a significant protective effect against the pathogenesis of heart failure. LncRNAs are emerging epigenetic regulators with(More)
BACKGROUND Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the(More)
The vascular smooth muscle cell (SMC)-specific isoform of alpha-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association(More)
OBJECTIVES We sought to determine the effects of PCSK9 variants on plasma low-density lipoprotein cholesterol (LDL-C) levels, severity of coronary atherosclerosis, and response to statin therapy in the Lipoprotein Coronary Atherosclerosis Study (LCAS) population. BACKGROUND Mutations in PCSK9 cause autosomal-dominant hypercholesterolemia. We hypothesized(More)
BACKGROUND Cardiac hypertrophy, the clinical hallmark of hypertrophic cardiomyopathy (HCM), is a major determinant of morbidity and mortality not only in HCM but also in a number of cardiovascular diseases. There is no effective therapy for HCM and generally for cardiac hypertrophy. Myocardial oxidative stress and thiol-sensitive signaling molecules are(More)
RATIONALE Mutations in the intercalated disc proteins, such as plakophilin 2 (PKP2), cause arrhythmogenic cardiomyopathy (AC). AC is characterized by the replacement of cardiac myocytes by fibro-adipocytes, cardiac dysfunction, arrhythmias, and sudden death. OBJECTIVE To delineate the molecular pathogenesis of AC. METHODS AND RESULTS Localization and(More)