Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 40, Issue 5, Pages 1006-1016Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0735-1097(02)02062-4
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R01 HL 59266] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available