The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes

Détails

ID Serval
serval:BIB_1D15B2084063
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes
Périodique
Diabetes
Auteur(s)
Pacher  P., Liaudet  L., Soriano  F. G., Mabley  J. G., Szabo  E., Szabo  C.
ISSN
0012-1797 (Print)
Statut éditorial
Publié
Date de publication
02/2002
Volume
51
Numéro
2
Pages
514-21
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Résumé
Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinone-based PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.
Mots-clé
Animals Diabetes Mellitus/genetics/*physiopathology Diabetes Mellitus, Experimental/physiopathology Endothelium, Vascular/*physiopathology Enzyme Activation/physiology Female Heart/*physiopathology Male Mice Mice, Inbred NOD Myocardium/enzymology Poly(ADP-ribose) Polymerases/*metabolism/physiology Rats Rats, Wistar Ventricular Function
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
03/03/2018 14:33
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