Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is a form of cell death that has been described as distinct from necrotic cell death. It is believed to be genetically programmed and occurs as a physiologic process in various organ systems of body. Although it has been tacitly believed that apoptosis does not occur in the terminally differentiated adult heart muscle cells, studies in endomyocardial biopsies from patients with dilated and ischemic cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histochemical evidence of apoptosis. It has been proposed that ventricular dilatation and neurohormonal activation during heart failure lead to upregulation of transcription factors, induce myocyte hypertrophy, and prepare the cell for entry into the cell cycle. However, terminally differentiated myocytes cannot divide, and failing to divide they undergo apoptosis. Initiation of apoptosis is associated with activation of upstream cascade, including the release of cytochrome c from mitochondria to cytoplasm and the processing of proteolytic caspases. The activation of caspases leads to fragmentation of various cytoplasmic proteins, including contractile proteins. However, the nuclear fragmentation and condensation is completed only rarely. It is hypothesized that the release of cytochrome c from mitochondria and cytoplasmic protein loss in a living heart muscle cell should lead to systolic dysfunction.
 ...
PMID:Apoptosis and cardiomyopathy. 1095 26

Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure.
 ...
PMID:Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes. 1178 5