Soriano, F.G., Virag, L., Jagtap, P., Szabo, E., Mabley, Jon, Liaudet, L., Marton, A., Hoyt, D.G., Murthy, K.G.K., Salzman, A.L., Southan, G.J. and Szabo, C. (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation Nature Medicine, 7 (1). pp. 108-113. ISSN 1546-170XFull text not available from this repository.
Diabetic patients frequently suffer from retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. The loss of endothelial function precedes these vascular alterations. Here we report that activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of endothelial dysfunction in diabetes. Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation. Treatment with a novel potent PARP inhibitor, starting after the time of islet destruction, maintained normal vascular responsiveness, despite the persistence of severe hyperglycemia. Endothelial cells incubated in high glucose exhibited production of reactive nitrogen and oxygen species, consequent single-strand DNA breakage, PARP activation and associated metabolic and functional impairment. Basal and high-glucose-induced nuclear factor-kappaB activation were suppressed in the PARP-deficient cells. Our results indicate that PARP may be a novel drug target for the therapy of diabetic endothelial dysfunction.
|Item Type:||Journal article|
|Subjects:||A000 Medicine > A300 Clinical Medicine|
|DOI (a stable link to the resource):||10.1038/83241|
|Faculties:||Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Disease Process > Diabetes|
|Depositing User:||editor spbs|
|Date Deposited:||08 Nov 2007|
|Last Modified:||26 Mar 2015 12:17|
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