Poly(ADP-ribose)polymerase 1 inhibition protects against age-dependent endothelial dysfunction

Clinical and Experimental Pharmacology & Physiology
Guang-Hao ZhangQing-Hua Lu

Abstract

Age-related endothelial dysfunction is closely associated with the local production of reactive oxygen species (ROS) within and in the vicinity of the vascular endothelium. Oxidant-induced DNA damage can activate the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), leading to endothelial dysfunction in various pathophysiological conditions. The present study aimed to investigate the role of PARP-1 in age-dependent changes in endothelial cell function and its underlying mechanism. Wild-type (WT) and PARP-1(-/-) mice were divided into young (2 months) and old (12 months) groups. Isolated aortic rings were suspended to record isometric tension to assess endothelial function. Nitric oxide (NO) production and content in plasma were detected by spectrophotometry. Superoxide (O2- production was detected by dihydroethidium. Expression of PARP-1, endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase (iNOS), and arginase-2 (Arg2) was assessed by western blot analysis. Endothelium-dependent relaxation in response to acetylcholine was lost in old WT, but not PARP-1(-/-) , mice. Endothelium-independent vasodilation was not impaired in aging mice. Production of O2- was greater in aging WT mice than young or aging PARP...Continue Reading

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Citations

Jul 1, 2017·Oxidative Medicine and Cellular Longevity·Douglas F DluzenMichele K Evans
Nov 12, 2018·Biochemical Pharmacology·Virginia CorreaniMaria d'Erme
Jul 25, 2021·International Journal of Molecular Sciences·Wioletta ZielińskaAlina Grzanka

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