title: Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.
abstract: 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.
authors.affiliation: Division of Cardiology, Heart Failure and Transplantation Center, MCP-Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102-1192, USA. jagat.narula@drexel.edu
authors.forename: J
authors.initials: J
authors.lastname: Narula
authors.forename: E
authors.initials: E
authors.lastname: Arbustini
authors.forename: Y
authors.initials: Y
authors.lastname: Chandrashekhar
authors.forename: M
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D051381:Rats; D013599:Systole / Q000502:physiology*