Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
Cardiovasc Res. 2011 Jul 1;91(1):27-36. doi: 10.1093/cvr/cvr042. Epub 2011 Feb 3.
Vascular peroxidase 1 (VPO1) is a newly identified haem-containing peroxidase that catalyses the oxidation of a variety of substrates by hydrogen peroxide (H(2)O(2)). Considering the well-defined effects of H(2)O(2) on the vascular remodelling during hypertension, and that VPO1 can utilize H(2)O(2) generated from co-expressed NADPH oxidases to catalyse peroxidative reactions, the aims of this study were to determine the potential role of VPO1 in vascular remodelling during hypertension.
The vascular morphology and the expression of VPO1 in arterial tissues of spontaneously hypertensive rats and Wistar-Kyoto rats were assessed. The VPO1 expression was significantly increased concomitantly with definite vascular remodelling assessed by evaluating the media thickness, lumen diameter, media thickness-to-lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats. In addition, in cultured rat aortic smooth muscle cells we found that the angiotensin II-mediated cell proliferation was inhibited by knockdown of VPO1 using small hairpin RNA. Moreover, the NADPH oxidase inhibitor, apocynin, and the hydrogen peroxide scavenger, catalase, but not the ERK1/2 inhibitor, PD98059, attenuated angiotensin II-mediated up-regulation of VPO1 and generation of hypochlorous acid.
VPO1 is a novel regulator of vascular smooth muscle cell proliferation via NADPH oxidase-H(2)O(2)-VPO1-hypochlorous acid-ERK1/2 pathways, which may contribute to vascular remodelling in hypertension.
血管过氧化物酶 1（VPO1）是一种新发现的含铁过氧化物酶，可通过过氧化氢（H₂O₂）催化多种底物的氧化。鉴于 H₂O₂在高血压期间对血管重塑的明确作用，以及 VPO1 可以利用共表达的 NADPH 氧化酶产生的 H₂O₂来催化过氧化物反应，本研究旨在确定 VPO1 在高血压期间血管重塑中的潜在作用。
评估了自发性高血压大鼠和 Wistar-Kyoto 大鼠动脉组织中的血管形态和 VPO1 的表达。VPO1 的表达明显增加，同时伴有动脉中层厚度、管腔直径、中层厚度与管腔直径比和动脉中层核平均面积的明确血管重塑评估。此外，在培养的大鼠主动脉平滑肌细胞中，我们发现使用短发夹 RNA 敲低 VPO1 可抑制血管紧张素 II 介导的细胞增殖。此外，NADPH 氧化酶抑制剂 apocynin 和过氧化氢清除剂 catalase，但不是 ERK1/2 抑制剂 PD98059，可减弱血管紧张素 II 介导的 VPO1 上调和次氯酸生成。
VPO1 是血管平滑肌细胞增殖的一种新型调节因子，通过 NADPH 氧化酶-H₂O₂-VPO1-次氯酸-ERK1/2 途径，可能导致高血压中的血管重塑。
