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

Autor:	Guang-hao Zhang, Min Chao, Juan Wang, Dong Ling Xu, We-li Cai, Qing-hua Lu, Ming-xiang Zhang, Jie Zheng, Min Gao, Long-hua Hui
Rok vydání:	2015
Předmět:	Male Aging medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Poly ADP ribose polymerase Active Transport Cell Nucleus Poly (ADP-Ribose) Polymerase-1 Nitric Oxide Synthase Type I Poly(ADP-ribose) Polymerase Inhibitors Nitric Oxide Gene Expression Regulation Enzymologic Nitric oxide Mice chemistry.chemical_compound Superoxides Enos Physiology (medical) Internal medicine Nitriles medicine Animals Humans Sulfones Endothelial dysfunction Cell Nucleus Pharmacology chemistry.chemical_classification Reactive oxygen species biology Chemistry Angiotensin II NF-kappa B medicine.disease biology.organism_classification Endothelial stem cell Nitric oxide synthase Endocrinology biology.protein Endothelium Vascular Proto-Oncogene Proteins c-akt Gene Deletion
Zdroj:	Clinical and Experimental Pharmacology and Physiology. 42:1266-1274
ISSN:	0305-1870
DOI:	10.1111/1440-1681.12484
Popis:	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-1(-/-) mice. eNOS expression was not affected by aging in WT or PARP-1(-/-) mice, but p-eNOS expression decreased and iNOS and Arg2 levels were upregulated only in aging WT mice. In conclusion, PARP-1 inhibition may protect against age-dependent endothelial dysfunction, potentially by regulating NO bioavailability via iNOS. Inhibition of PARP-1 may help in vascular aging prevention.
Databáze:	OpenAIRE
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