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Involvement of VPO1in the Endothelial Dysfunction in Hypertension

Author: PengHaiYang
Tutor: ZhangGuoGang
School: Central South University
Course: Clinical
Keywords: Angiotensin Ⅱ vascular peroxidase oxidative stress endothelial dysfunction
CLC: R544.1
Type: Master's thesis
Year: 2013
Downloads: 13
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OBJECTIVE:To explore the relationship of VPO1expression and the endothelial dysfunction in spontaneously hypertensive rats (SHR) and Ang Ⅱ-induced Human umbilical vein endothelial cells (HUVECs), and the possible mechanism.METHODS:Ten20-week-old male SHRs served as SHR group, and ten age and sex matched Wistar Kyoto rats (WKY) were selected as control group. Endothelial-dependent relaxation of thoracic aorta, aortal VPO1, Nox4, eNOS expression, and VPO1, H2O2, NO in plasma were determined. HUVECs were incubated in Ang Ⅱ, in the presence or absence of Nox-specific inhibitor DPI, H202hydolytic enzyme Catalase, or VPO-specific inhibitor ABAH. Cellular VPO1, Nox4, and eNOS expression were measured, as well as H2O2, HOCl, and NO concentration. Inhibition of HOCl to eNOS was also determined.RESULTS:Aortal VPO1and Nox4expression were increased in SHRs, as well as VPO1and H2O2in plasma. Aortal eNOS expression and NO concentration in plasma of SHRs were decreased, and the endothelial-dependent diastolic function was impaired. In cultured HUVECs, Ang Ⅱ increased expression of VPO1in a concentration and time-dependent manner. Incubation of Ang II elevated level of H2O2and HOCl, and decreased the expression of eNOS and NO production. Treatment of HOCl directly depressed the expression of eNOS. Nox4expression was inhibited by DPI, while H2O2level was decreased by DPI and Catalase. The decreased expression of VPO1by DPI, Catalase and ABAH led to down-regulated HOC1production, which elevated the expression of eNOS and NO production.CONCLUTION:VPO1may play a critical role in the endothelial dysfunction in hypertension. Activated expression of VPO1by Ang II can utilize Nox4-derived H2O2to produce HOCl, which depresses the expression of eNOS, leading to the endothelial dysfunction.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Abnormal blood pressure > Hypertension
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