title: Cardioprotective effects of poly(ADP-ribose) polymerase inhibition.
abstract: Free radical and oxidant production in cardiac myocytes during ischemia/reperfusion, cardiomyopathy, cardiotoxic drug exposure and ageing leads to DNA strand-breakage which activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and initiates an energy consuming, inefficient cellular metabolic cycle with transfer of the ADP-ribosyl moiety of NAD+ to protein acceptors. These processes lead to the functional impairment of the myocytes and promote myocyte death. During the last decade a growing number of experimental studies demonstrated the beneficial effects of PARP inhibition in cell cultures through rodent models and more recently in pre-clinical large animal models of regional and global ischemia/reperfusion injury and various forms of heart failure. The current article provides an overview of the experimental evidence implicating PARP as a pathophysiological modulator of cardiac myocyte injury in vitro and in vivo.
authors.affiliation: Inotek Pharmaceuticals Corporation, Beverly, MA 01915, USA. szabocsaba@aol.com
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000209:etiology; D015687:Cell Hypoxia; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020011:Protective Agents; D011065:Poly(ADP-ribose) Polymerases