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A lthough low levels of high-density lipoprotein cholesterol (HDL-C) represent a strong independent risk marker inversely associated with cardiovascular disease (CVD), large interventional trials have failed to translate the increases in HDL-C into reductions in cardiovascular events. As HDL plasma levels represent a pool of the different HDL subfractions,(More)
A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22(phox), which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H)(72)-->tyrosine (Y) mutation in p22(phox) with the severity and(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)
Myocardial contractility is generally believed to be increased in hypertrophic cardiomyopathy. I propose the opposite--that cardiac myocyte contractility is decreased in this disorder. Accordingly, the contractile deficit provides the primary stimulus for increased expression of trophic factors in the heart, which leads to hypertrophy, interstitial(More)
BACKGROUND Human hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis. The genetic basis of HCM is largely known; however, the molecular mediators of cardiac phenotypes are unknown. METHODS AND RESULTS We show myocardial(More)
We determined the distribution frequency of angiotensin converting enzyme (ACE) polymorphism in 100 patients with hypertrophic cardiomyopathy and 106 of their unaffected siblings and offspring. The distribution of ACE genotypes was different in the two groups: allele D frequency of 0.69 in patients and 0.57 in relatives (p = 0.021). The frequency of allele(More)
BACKGROUND Systolic (Sa) and diastolic (Ea) myocardial velocities measured by tissue Doppler (TD) imaging (TDI) recently were shown to be decreased in subjects who have mutations causing hypertrophic cardiomyopathy (HCM) but who do not have left ventricular (LV) hypertrophy. By studying these subjects at a later date, we sought to determine whether TDI(More)
Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG)(More)
BACKGROUND Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and(More)