Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation
Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation
复制标题
血管过氧化物酶 1 参与血管紧张素 II 诱导的血管平滑肌细胞增殖。
DOI：
10.1093/cvr/cvr042
复制
发表时间：
2011-07-01
影响因子：
10.8
通讯作者：
Zhang, Guogang
中科院分区：
文献类型：
--
作者：
Shi, Ruizheng;Hu, Changping;Zhang, Guogang
旨在
血管过氧化物酶1（VPO 1）是一种新发现的含血红素的过氧化物酶，可催化多种底物被过氧化氢（H（2）O（2））氧化。考虑到H2 O2在高血压血管重构中的明确作用，以及VPO 1可以利用共表达的NADPH氧化酶产生的H2 O2催化过氧化反应，本研究的目的是确定VPO 1在高血压血管重构中的潜在作用。
方法和结果
观察自发性高血压大鼠和Wistar-Kyoto大鼠的血管形态及血管组织中VPO 1的表达。VPO 1的表达显着增加伴随着明确的血管重塑评估通过评估中膜厚度，管腔直径，中膜厚度与管腔直径比和平均核面积在动脉介质在自发性高血压大鼠。此外，在培养的大鼠主动脉平滑肌细胞中，我们发现，血管紧张素II介导的细胞增殖抑制VPO 1敲低使用小发夹RNA。此外，NADPH氧化酶抑制剂，夹竹桃素，和过氧化氢清除剂，过氧化氢酶，但不是ERK 1/2抑制剂，PD 98059，衰减血管紧张素II介导的上调VPO 1和次氯酸的产生。
结论
VPO 1通过NADPH氧化酶-H2 O2-VPO 1-次氯酸-ERK 1/2途径调节血管平滑肌细胞增殖，可能参与高血压血管重构。
AIMS
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.
METHODS AND RESULTS
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.
CONCLUSION
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.