Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure

Pacher, P., Liaudet, L., Mabley, J.G., Komjati, K. and Szabo, C. (2002) Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure Journal of the American College of Cardiology, 40 (5). pp. 1006-1016. ISSN 0735-1097

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Abstract

Objectives : We investigated the effects of a novel ultrapotent poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, PJ34, on cardiac and endothelial dysfunction in a rat model of chronic heart failure (CHF). Background : Overactivation of the nuclear enzyme PARP importantly contributes to the development of cell dysfunction and tissue injury in various pathophysiologic conditions associated with oxidative stress, including myocardial reperfusion injury, heart transplantation, stroke, shock, and diabetes. Methods : Chronic heart failure was induced in Wistar rats by chronic ligation of the left anterior descending coronary artery. Left ventricular (LV) function and ex vivo vascular contractility and relaxation were measured 10 weeks after the surgery. Nitrotyrosine (NT) formation and PARP activation were detected by immunohistochemistry. Results : Chronic heart failure induced increased NT formation and PARP activation in the myocardium and intramural vasculature, depressed LV performance, and impaired vascular relaxation of aortic rings. PJ34 significantly decreased myocardial PARP activation but not NT formation, and improved both cardiac dysfunction and vascular relaxation. Conclusions : Poly(ADP-ribose) polymerase inhibition represents a novel approach for the experimental treatment of CHF.

Item Type:Journal article
Subjects:B000 Health Professions > B200 Pharmacology Toxicology and Pharmacy > B210 Pharmacology and Therapeutics
DOI (a stable link to the resource):10.1016/S0735-1097(02)02062-4
Faculties:Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
ID Code:868
Deposited By:editor spbs
Deposited On:01 Dec 2006
Last Modified:17 Apr 2014 13:58

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