Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation

Abstract

Vascular peroxidase 1 (VPO1) is a newly identified haem-containing peroxidase that catalyses the oxidation of a variety of substrates by hydrogen peroxide (H₂O₂). Considering the well-defined effects of H₂O₂ on the vascular remodelling during hypertension, and that VPO1 can utilize H₂O₂ 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–H₂O₂–VPO1–hypochlorous acid–ERK1/2 pathways, which may contribute to vascular remodelling in hypertension.