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

Détails

ID Serval
serval:BIB_4685559B6081
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure
Périodique
Journal of the American College of Cardiology
Auteur(s)
Pacher  P., Liaudet  L., Mabley  J., Komjati  K., Szabo  C.
ISSN
0735-1097 (Print)
Statut éditorial
Publié
Date de publication
09/2002
Volume
40
Numéro
5
Pages
1006-16
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep 4
Résumé
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.
Mots-clé
Animals Enzyme Activation Enzyme Inhibitors/*pharmacology Heart Failure, Congestive/*drug therapy/physiopathology Immunohistochemistry Male Phenanthrenes/*pharmacology Poly(ADP-ribose) Polymerases/*antagonists & inhibitors Rats Rats, Wistar Tyrosine/*analogs & derivatives/biosynthesis Vasomotor System/drug effects Ventricular Function, Left/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 18:00
Dernière modification de la notice
08/05/2019 17:57
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