Mechanisms of disease: apoptosis in heart failure--seeing hope in death.
Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome c release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome c from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of 'apoptosis interruptus' could allow development of novel strategies to reverse or attenuate heart failure.
Narula
Jagat
J
Division of Cardiology, University of California, Irvine School of Medicine, 101 The City Drive, Building 53, Mail Route 81, Orange, CA 92868, USA. narula@uci.edu
Haider
Nezam
N
Arbustini
Eloisa
E
Chandrashekhar
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002303:Cardiac Output, Low / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
D011480:Protease Inhibitors; D045304:Cytochromes c; D020169:Caspases