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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that environmentally or genetically induced changes in the intracellular proteins that compose the cytoskeleton can contribute to heart failure. Because neonatal right ventricular myocytes are immature and are in the process of significant cytoskeletal change, we hypothesized that they may be particularly susceptible to pressure stress. Newborn calves exposed to hypobaric hypoxia (barometric pressure = 430 mmHg) for 14 days developed severe pulmonary hypertension (pulmonary arterial pressure = 101 +/- 6 vs. 27 +/- 1 mmHg) and right heart failure compared with age-matched controls. Light microscopy showed partial loss of myocardial striations in the failing neonatal right but not left ventricles and in neither ventricle of adolescent cattle dying of altitude-induced right heart failure. In neonatal calves, immunohistochemical analysis of the cytoskeletal proteins (vinculin, metavinculin, desmin, vimentin, and cadherin) showed selectively, within the failing right ventricles, patchy areas characterized by loss and disorganization of costameres and intercalated discs. Within myocytes from the failing ventricles, vinculin and desmin were observed to redistribute diffusely within the cytosol, metavinculin appeared in disorganized clumps, and vimentin immunoreactivity was markedly decreased. Western blot analysis of the failing right ventricular myocardium showed, compared with control, vinculin and desmin to be little changed in total content but redistributed from insoluble (structural) to soluble (cytosolic) fractions; metavinculin total content was markedly decreased, tubulin content increased, particularly in the structural fraction, and cadherin total content and distribution were unchanged. We conclude that hypoxic pulmonary hypertensive-induced neonatal right ventricular failure is associated with disorganization of the cytoskeletal architecture.
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PMID:Myocyte cytoskeletal disorganization and right heart failure in hypoxia-induced neonatal pulmonary hypertension. 1099 4

Production of genome sequence has recently skyrocketed with many advances in the understanding and etiology of certain diseases. Researchers have localized a region of the human genome that plays a role in determining a persons susceptibility to myocardial infarction. A new apolipoprotein gene that influences triglyceride levels in humans is also described. A recent study from Finland showed that certain families are likely to carry a genetic form of insulin resistance syndrome that predisposes them to accelerated atherosclerosis. Researchers identified 3 mutations in the gene producing a protein called metavinculin, which appears to be linked to abnormalities in cellular structures and function in patients with dilated cardiomyopathy. Gene therapy has emerged as a genuine therapeutic option with the potential to alter the manner in which cardiologists manage the 2 most common cardiac disorders--coronary artery disease and congestive heart failure. Along with angiogenesis and gene therapy, cell transplantation is one of the newest treatment modalities proposed to improve the outcome of patients with cardiac failure. Two major advances in stem cell therapy for cardiovascular disease were published recently. They demonstrate how bone marrow stem cells can regenerate myocardium in the infarct area of a mouse heart. A German Cardiologist has for the first time successfully transplanted a patients own stem cells in an infracted area in the heart. This review summarizes the current knowledge of the genetic associations with cardiac diseases.
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PMID:Genetics and heart disease. 1259 Feb 66

The main cause of death globally remains debilitating heart conditions, such as dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which are often due to mutations of specific components of adhesion complexes. Vinculin regulates these complexes and plays essential roles in intercalated discs that are necessary for muscle cell function and coordinated movement and in the development and function of the heart. Humans bearing familial or sporadic mutations in vinculin suffer from chronic, progressively debilitating DCM that ultimately leads to cardiac failure and death, whereas autosomal dominant mutations in vinculin can also provoke HCM, causing acute cardiac failure. The DCM/HCM-associated mutants of vinculin occur in the 68-residue insert unique to the muscle-specific, alternatively spliced isoform of vinculin, termed metavinculin (MV). Contrary to studies that suggested that phosphoinositol-4,5-bisphosphate (PIP2) only induces vinculin homodimers, which are asymmetric, we show that phospholipid binding results in a domain-swapped symmetric MV dimer via a quasi-equivalent interface compared with vinculin involving R975. Although one of the two PIP2 binding sites is preserved, the symmetric MV dimer that bridges two PIP2 molecules differs from the asymmetric vinculin dimer that bridges only one PIP2 Unlike vinculin, wild-type MV and the DCM/HCM-associated R975W mutant bind PIP2 in their inactive conformations, and R975W MV fails to dimerize. Mutating selective vinculin residues to their corresponding MV residues, or vice versa, switches the isoform's dimeric constellation and lipid binding site. Collectively, our data suggest that MV homodimerization modulates microfilament attachment at muscular adhesion sites and furthers our understanding of MV-mediated cardiac remodeling.
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PMID:Differential lipid binding of vinculin isoforms promotes quasi-equivalent dimerization. 2750 91