Poly(ADP-ribose) polymerase 1 inhibition protects against age-dependent endothelial dysfunction
Poly(ADP-ribose) polymerase 1 inhibition protects against age-dependent endothelial dysfunction
复制标题
聚（ADP-核糖）聚合酶 1 抑制可预防年龄依赖性内皮功能障碍
DOI：
10.1111/1440-1681.12484
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发表时间：
2015
影响因子：
2.9
通讯作者：
Lu Qing-hua
中科院分区：
文献类型：
--
作者：
Zhang Guang-hao;Chao Min;Hui Long-hua;Xu Dong Ling;Cai We-li;Zheng Jie;Gao Min;Zhang Ming-xiang;Wang Juan;Lu Qing-hua
年龄相关的内皮功能障碍与血管内皮内及其附近活性氧（ROS）的局部产生密切相关。氧化剂诱导的 DNA 损伤可以激活核酶聚（ADP-核糖）聚合酶 1 (PARP-1)，导致各种病理生理条件下的内皮功能障碍。本研究旨在探讨PARP-1在内皮细胞功能年龄依赖性变化中的作用及其潜在机制。野生型 (WT) 和 PARP-1−/− 小鼠被分为年轻组（2 个月）和老年组（12 个月）。悬挂分离的主动脉环以记录等长张力以评估内皮功能。采用分光光度法检测血浆中一氧化氮（NO）的产生和含量。通过二氢乙锭检测超氧化物（的产生）。通过蛋白质印迹分析评估 PARP-1、内皮一氧化氮合酶 (eNOS)、诱导一氧化氮合酶 (iNOS) 和精氨酸酶-2 (Arg2) 的表达。在老年 WT 小鼠中，对乙酰胆碱响应的内皮依赖性松弛消失，但 PARP-1−/− 小鼠却没有。在衰老小鼠中，内皮独立的血管舒张并未受损。衰老 WT 小鼠中的 eNOS 表达量高于年轻或衰老的 PARP-1−/− 小鼠，但 p-eNOS 表达下降，并且仅在衰老 WT 小鼠中 iNOS 和 Arg2 水平上调。 总之，PARP-1 抑制可能通过抑制 PARP-1 调节 NO 生物利用度来预防年龄依赖性内皮功能障碍。预防血管老化。
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 ( 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 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.