Objective To determine the role of Vascular peroxide 1(VPO1), a newly identified haem-containing peroxidases in vascular remodelling in hypertension.
Methods The carotid arterial intima-media thickness in patients with essential hypertension and the Media thickness, lumen diameter, media thickness/lumen diameter ratio, mean nuclear area in artery media in spontaneously hypertensive rats (SHRs) were assessed while the plasma level of VPO1 in patients and the expression of VPO1 in arterial tissues was measured. Cultured human aorta vascular smooth muscle cells were treated with ANGII, and the proliferation activity, VPO1 expression, H2O2 and HOCL level were examined. The effect of VPO1 RNA interference, apocynin, catalase and PD98059 on VPO1 expression and the proliferation activity of cells were observed.
Results The VPO1 level/expression was significantly increased in patients with essential hypertension and in spontaneously hypertensive rats concomitant with definite vascular remolding by evaluating the intima-media thickness, pressure-strain elastic modulus and stiffness index of carotid artery in patients, as well as the media thickness, lumen diameter, media thickness/lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats. The angiotension II-stimulated cell proliferation of human aorta smooth muscle cells was inhibited by knockdown of VPO1 using small hairpin RNA. Moreover, the NADPH oxidase inhibitor, apocynin, the hydrogen peroxide scavenger, catalase, but not the ERK1/2 inhibitor, PD98059 attenuated Ang II-mediated upregulation of VPO1 and generation of hypochlorous acid.
Conclusions VPO1 is a novel regulator of vascular smooth muscle cell proliferation via NADPH oxidase/H2O2/VPO1/ERK1/2 pathways and plays an important role in vascular remodelling during hypertension.