title: Inhibition of myocardial apoptosis as a therapeutic target in cardiovascular disease prevention: focus on caspase inhibition.
abstract: Apoptosis is a type of programmed cell death that is evident during embryonic development and normal tissue turnover. When the apoptotic activity extends beyond physiologic limits, it can determine and/or contribute to those pathologic states characterized by excessive cell loss and impairment of organ function. The clinical development of caspase inhibitors may represent a potential therapeutic strategy for influencing the onset and progression of ventricular dysfunction to terminal failure. This article focuses on the caspase cascade, a fundamental enzymatic system for apoptotic cell death. Caspases do not constitute the death signals, but are implicated in their transmission. These cytoplasmic cysteine proteases have a dual role in apoptosis. Caspases can operate as initiators, activating an endonuclease that catalyzes deoxyribonucleic acid fragmentation. Alternatively, caspases can act as effectors, participating in the total disassembly of cell structures. For example, apoptosis represents the principal form of myocyte death in the region of an acute myocardial infarction. In addition, apoptosis in the region bordering the infarct can influence the development of ischemic cardiomyopathy and ventricular dilation.
authors.affiliation: Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, New York 10595, USA.
authors.forename: N
authors.initials: N
authors.lastname: Guttenplan
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: W H
authors.initials: WH
authors.lastname: Frishman
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D009206:Myocardium / Q000201:enzymology*; D016896:Treatment Outcome
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020169:Caspases