Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats.
Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats.
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DOI：
10.1016/j.bbrc.2013.09.012
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发表时间：
2013-10
影响因子：
3.1
通讯作者：
Lizhen Yang;Yongping Bai;Nian‐sheng Li;Changping Hu;Jun Peng;G. Cheng;Guogang Zhang;Ruizheng Shi-Ruizhe
中科院分区：
文献类型：
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作者：
Lizhen Yang;Yongping Bai;Nian‐sheng Li;Changping Hu;Jun Peng;G. Cheng;Guogang Zhang;Ruizheng Shi-Ruizhe
活性氧（ROS）会导致内皮功能障碍，从而导致高血压的发病机制。血管过氧化物酶 1 (VPO1) 可以利用 ROS 催化过氧化反应，可能增强内皮功能障碍。本研究旨在确定 VPO1 与内皮功能障碍和高血压的关系。将 64 只自发性高血压大鼠 (SHR) 和 64 只年龄匹配、体重控制正常的 Wistar-Kyoto 大鼠 (WKY) 随机分组，并在 5、8、13 和 20 周龄时进行研究（每组 16 只）。观察血压和主动脉环中乙酰胆碱的血管舒张反应。通过定量逆转录PCR和蛋白质印迹分析评估主动脉中VPO1和内皮NO合酶(eNOS)的表达。本研究还测定了过氧化氢 (H2O2) 和 NO 的血浆浓度、NOX 活性、次氯酸 (HOCl) 产生以及主动脉匀浆中的 3-硝基酪氨酸含量。随着 SHR 大鼠高血压的发展，与 8、13 和 20 周龄的 WKY 大鼠相比，VPO1 表达上调，NOX 活性、HOCl 产生、3-硝基酪氨酸含量和血浆 H2O2 水平显着增加。相比之下，SHR 中血液 NO 水平降低，主动脉对乙酰胆碱的松弛程度恶化。高血压发生过程中VPO1过度表达，并伴有内皮功能障碍、NO水平降低、NOX和ROS活性升高，表明VPO1基因与高血压之间存在明确的联系。 VPO1 可能通过涉及 NOX-H2O2-VPO1-HOCl 或 JNK/p38 MAPK 的信号通路导致高血压，但仍需要进一步研究来确定确切的机制。
Reactive oxygen species (ROS) contributes to endothelial dysfunction that is involved in the pathogeneses of hypertension. Vascular peroxidase 1 (VPO1) can utilize ROS to catalyze peroxidative reactions, possibly enhancing endothelial dysfunction. This study is to identify VPO1’s involvement in endothelial dysfunction and hypertension. Sixty-four spontaneously hypertensive rats (SHRs) and 64 age-matched, bodyweight controlled normotensive Wistar–Kyoto rats (WKYs) were randomly grouped and studied at the age of 5, 8, 13 and 20 weeks (16 animals, each). Blood pressure and vasodilator responses to acetylcholine in aortic rings were observed. The expressions of VPO1 and endothelial NO synthase (eNOS) in aortas were assessed by quantitative reverse transcription-PCR and western blotting analysis. Plasma concentrations of hydrogen peroxide (H2O2) and NO, NOX activity, hypochlorous acid (HOCl) production, and 3-nitrotyrosine content in aortic homogenates were also determined in this study. Along with the development of hypertension in SHR rats, VPO1 expression was up-regulated together with a significant increase in NOX activity, HOCl production, 3-nitrotyrosine content, and plasma H2O2level compared with WKYs at 8, 13 and 20 weeks of age. In contrast, blood NO levels were decreased and aortic relaxation to acetylcholine was deteriorated in SHRs. The over-expression of VPO1 during the development of hypertension, accompanied by the endothelial dysfunction, the decreased NO levels, the elevated NOX and ROS activities, indicates a clear connection between VPO1 gene and hypertension. VPO1 may pathogenetically contribute to hypertension via signal pathways involving NOX–H2O2–VPO1–HOCl or JNK/p38 MAPK although further studies are needed to determine the precise mechanisms.