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001-es BibID:BIBFORM014262
Első szerző:Pacher Pál
Cím:The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes / Pacher, P., Liaudet, L., Soriano, F. G., Mabley, J. G., Szabo, E., Szabo, C.
Dátum:2002
ISSN:0012-1797 (Print)
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
külföldön készült közlemény
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
Megjelenés:Diabetes. - 51 : 2 (2002), p. 514-521. -
További szerzők:Liaudet, Lucas Soriano, Francisco Garcia Mabley, Jon G. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Szabó Csaba
Internet cím:elektronikus változat
DOI
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