PARP inhibition and postinfarction myocardial remodeling

Robert Halmosi, Laszlo Deres, Roland Gal, Krisztian Eros, Balazs Sumegi, Kalman Toth

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)S52-S59
JournalInternational Journal of Cardiology
Volume217
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Ischemia–reperfusion injury
  • Myocardial infarction
  • PARP-inhibition
  • Postinfarction remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'PARP inhibition and postinfarction myocardial remodeling'. Together they form a unique fingerprint.

  • Cite this