Apoptosis and cardiomyopathy

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 diff erentiated adult heart muscle cells, studies in endomyocardial biopsies fro m patients with dilated and ischemic cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantat ion have demonstrated histochemical evidence of apoptosis, It has been prop osed that ventricular dilatation and neurohormonal activation during heart failure lead to upregulation of transcription factors, induce myocyte hyper trophy, and prepare the cell for entry into the cell cycle. However, termin ally differentiated myocytes cannot divide, and failing to divide they unde rgo apoptosis, Initiation of apoptosis is associated with activation of ups tream cascade, including the release of cytochrome c from mitochondria to c ytoplasm and the processing of proteolytic caspases. The activation of casp ases leads to fragmentation of Various cytoplasmic proteins, including cont ractile proteins. However, the nuclear fragmentation and condensation is co mpleted only rarely, It is hypothesized that the release of cytochrome c fr om mitochondria and cytoplasmic protein loss in a living heart muscle cell should lead to systolic dysfunction, (C) 2000 Lippincott Williams & Wilkins , Inc.