Familial hypertrophic cardiomyopathy: functional effects of myosin mutation R723G in cardiomyocytes.

Familial Hypertrophic Cardiomyopathy (FHC) is frequently caused by mutations in the β-cardiac myosin heavy chain (β-MyHC). To identify changes in sarcomeric function triggered by such mutations, distinguishing mutation effects from other functional alterations of the myocardium is essential. We previously identified a direct effect of mutation R723G (MyHC723) on myosin function in slow Musculus soleus fibers.

Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level.

Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT-HF).

Aims: Previous experimental and clinical studies have consistently suggested that right ventricular (RV) apical pacing has important adverse effects. Ventricular pacing (VP), however, is required, and cannot be reduced in many patients with atrioventricular (AV) block. The PREVENT-HF study was an international randomized trial that explored differences in left ventricular (LV) remodelling during RV apical vs.

The left and right ventricle of a patient with a R723G mutation of the beta-myosin heavy chain and severe hypertrophic cardiomyopathy show no differences in the expression of myosin mRNA.

Background: In familial hypertrophic cardiomyopathy (FHC), asymmetric left ventricular (LV) hypertrophy has been considered to be the predominant phenotypic expression, whereas right ventricular (RV) involvement is still ambiguous. In most cases, the right ventricle remains unaffected until secondary pulmonary hypertension develops. Several FHC-causing mutations of genes encoding sarcomere-related proteins have been identified which are transmitted in an autosomal-dominant manner.

Quantification of mutant versus wild-type myosin in human muscle biopsies using nano-LC/ESI-MS.

A liquid chromatography/electrospray ionization mass spectrometry (nano-LC/ESI-MS) approach is described by which abundance of proteins (e.g., of beta-myosin heavy chain; MW 223 kDa) carrying a point mutation can be determined in tissue samples where the mutant protein is coexpressed with its wild-type forms.

Correlation between insulin resistance surrogates and echocardiographic findings in asymptomatic patients with morbid obesity: a cross-sectional study.

Objective: To assess the relationship between insulin resistance (IR) and left ventricular diastolic dysfunction (LVDD) in asymptomatic patients with morbid obesity (MO).

Methods: The study cohort consisted of 231 patients (165 women and 66 men) with MO (mean body mass index [BMI] of 46.0 kg/m2) and a control group of 93 age-and sex-matched apparently healthy control subjects (56 women and 37 men; mean BMI of 24.

Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: rationale and design of the PREVENT-HF study.

Aims: Right ventricular (RV) pacing has been shown to cause heart failure symptoms in patients with and without previous systolic left ventricular (LV) dysfunction. The aim here was to evaluate the preventive effect of biventricular pacing vs. RV apical pacing in patients with indication for permanent ventricular pacing.

Hypertrophic cardiomyopathy-related beta-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells.

Disease-causing mutations in cardiac myosin heavy chain (beta-MHC) are identified in about one-third of families with hypertrophic cardiomyopathy (HCM). The effect of myosin mutations on calcium sensitivity of the myofilaments, however, is largely unknown. Because normal and mutant cardiac MHC are also expressed in slow-twitch skeletal muscle, which is more easily accessible and less subject to the adaptive responses seen in myocardium, we compared the calcium sensitivity (pCa(50)) and the steepness of force-pCa relations (cooperativity) of single soleus muscle fibers from healthy individuals and from HCM patients of three families with selected myosin mutations.

[Hypertrophic cardiomyopathy. Genetic basis and clinical implications].

Thanks to advances in molecular biology during the last decade, the etiology of hypertrophic cardiomyopathy has been elucidated. Although more than 150 causal mutations of 9 genes that encode contractile proteins have been identified, many of the pathogenetic mechanisms remain unclear. In this review we discuss the current state of knowledge of the functional effects of some mutations, particularly two of the most lethal beta-myosin mutations -Arg403Gln and Arg723Gly (Barcelona mutation)- and their contributions to the pathogenesis of hypertrophy, sudden death and ischemia.

[Late T-lymphocyte and monocyte activation in coronary restenosis. Evidence for a persistent inflammatory/immune mechanism?].

Aims: This study was made to determine if restenosis after percutaneous coronary angioplasty is associated with acute or chronic inflammatory/immunologic activity, and explored possible relationships with latent infection.

Patients And Method: Forty-six consecutive patients underwent elective PTCA and 6 months of angiographic follow-up. Peripheral venous blood samples were obtained at baseline, 24-48 h, and 4-6 months post-intervention.

[Genes and coronary heart disease].

The causes of atherosclerotic cardiovascular disease have been intensely scrutinized for the last few decades. Since the classic risk factors have been found to be incomplete predictors of the disease, additional risk factors based on molecular genetics are now being sought. Polymorphisms are gene variations that have only modest effects on the function of coded proteins or enzymes.