Vascular peroxidase 1 up regulation by angiotensin II attenuates nitric oxide production through increasing asymmetrical dimethylarginine in HUVECs
Vascular peroxidase 1 up regulation by angiotensin II attenuates nitric oxide production through increasing asymmetrical dimethylarginine in HUVECs
复制标题
血管紧张素 II 上调血管过氧化物酶 1，通过增加 HUVEC 中的不对称二甲基精氨酸来减弱一氧化氮的产生。
DOI：
10.1016/j.jash.2016.06.036
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发表时间：
2016-09-01
影响因子：
--
通讯作者：
Shi, Ruizheng
中科院分区：
文献类型：
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作者：
Peng, Haiyang;Chen, Luyao;Shi, Ruizheng
Asymmetric dimethylarginine (ADMA), the endogenous inhibitor of nitric oxide synthase, contributes to endothelial dysfunction and subsequent cardiovascular events including hypertension. Vascular peroxidase 1 (VPO1) is a novel heme-containing peroxidase that uses hydrogen peroxide (H2O2) generated from co-expressed nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to catalyze peroxidative reactions. Our previous study revealed a clear connection between VPO1 gene expression and endothelial dysfunction in spontaneously hypertensive rats. In the present study, we explored whether VPO1 participates in endothelial dysfunction during hypertension by increasing ADMA production. Spontaneously hypertensive rats displayed impaired endothelium-dependent relaxation, decreased eNOS expression and nitric oxide production, significantly increased VPO1 expression in both plasma and aorta tissue, and an increased ADMA level in plasma. In cultured endothelial cells, angiotensin II increased the ADMA level by inhibiting dimethylarginine dimethylaminohydrolase activity, which was inhibited by knockdown of VPO1 using small hairpin RNA. Moreover, the NADPH oxidase inhibitor and the hydrogen peroxide scavenger attenuated angiotensin II-mediated up-regulation of VPO1 and generation of hypochlorous acid. Furthermore, VPO1-derived hypochlorous acid suppressed recombinant dimethylarginine dimethylaminohydrolase activity and increased ADMA production. VPO1 plays a critical role in ADMA production via H2O2-VPO1-hypochlorous acid pathways, which may contribute to endothelial dysfunction in hypertension. (C) 2016 American Society of Hypertension. All rights reserved.
