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Myocardial apoptosis in the overloaded and the aging heart: a critical role of mitochondria? |
European Cytokine Network. Volume 9, Number 4, 693-6, December 1998, Conférence : Cytokines and apoptosis in the cardiovascular system Halle (Germany) 26-27 February 1998
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 Free Article
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Author(s) : H. Heinrich and J. Holtz |
Summary : Myocardial apoptosis is a typical feature of human terminal cardiac failure. However, the quantitative role of the apoptotic process for the progression of failure and the stimuli inducing programmed cell death of cardiomyocytes in the failing heart are unknown. Acute stretch of isolated papillary muscle in vitro induces apoptosis [1], but distension of the extent reported in these in vitro experiments is unlikely to occur in vivo, even in terminal failure. Chronically overloaded myocardium has phenotype changes with an apoptotic potential, such as alterations in "death-domain" containing receptor systems [2], in apoptosis modulating proteins of the Bcl-2 family [3] and in the cardiac angiotensin system (see [4]), and these alterations are partially normalized by hemodynamic unloading in heart failure patients with an implanted cardiac assist device [5]. However, a direct role of these phenotype changes for the induction of apoptosis could not yet been demonstrated. The proteolytic activation of a cascade of caspases (a class of aspartate-specific proteases) is considered as the effector machinery of programmed cell death. A critical step in the activation of this terminal apoptotic cascade is the release of proapoptotic factors from mitochondria (see below). Until recently, disturbances in mitochondrial function have been seen mainly in the context of a disturbed cellular energy production. Disturbed mitochondrial function as a starting mechanism for the execution of cellular apoptosis is a new point of view, which will be discussed here in the context of cardiac failure. |
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