title: PARP inhibition and postinfarction myocardial remodeling.
abstract: Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling.
authors.affiliation: 1st Department of Medicine, Division of Cardiology, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Halmosi
authors.affiliation: 1st Department of Medicine, Division of Cardiology, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Deres
authors.affiliation: 1st Department of Medicine, Division of Cardiology, University of Pecs, Pecs, Hungary.
authors.forename: Roland
authors.initials: R
authors.lastname: Gal
authors.affiliation: 1st Department of Medicine, Division of Cardiology, University of Pecs, Pecs, Hungary; Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Eros
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary; MTA-PTE, Nuclear and Mitochondrial Interactions Research Group, Pecs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.affiliation: 1st Department of Medicine, Division of Cardiology, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary; MTA-PTE, Nuclear and Mitochondrial Interactions Research Group, Pecs, Hungary. Electronic address: toth.kalman@pte.hu.
authors.forename: Kalman
authors.initials: K
authors.lastname: Toth
mesh_terms: D006333:Heart Failure / Q000517:prevention & control*; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000401:mortality; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors
keywords: Ischemia–reperfusion injury; Myocardial infarction; PARP-inhibition; Postinfarction remodeling