title: Role of cell death in the progression of heart failure.
abstract: All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria-mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease.
authors.affiliation: St. Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Moe
authors.affiliation: The Molecular Cardiology and Neuromuscular Institute, 75 Raritan Avenue. 2nd. Floor, Suite 225, Highland Park, NJ, 08904, USA. tmci@att.net.
authors.forename: José
authors.initials: J
authors.lastname: Marín-García
mesh_terms: D016923:Cell Death; D018450:Disease Progression; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology
keywords: Apoptosis; Autophagy; Cell death; Extrinsic apoptotic pathways; Intrinsic apoptotic pathways; Mitophagy; Necrosis