Objectives Hypoxia could induce pulmonary arterial smooth muscle cells (PASMCs) proliferation via hydrogen peroxide (H2O2)-induced oxidative stress. Our previous research had demonstrated that vascular peroxidase 1 (VPO1) could utilise hydrogen peroxide generated from co-expressed NADPH oxidase to produce hypochlorous acid (HOCl) and catalyse peroxidative reactions. This study was aimed to determine the potential role of VPO1 in the proliferation of PASMCs in pulmonary arterial hypertension.
Methods Primary rat PASMCs were extracted and treated with hypoxia (3% O2). The proliferation activity of PASMCs, the expression of VPO1 and ID1 expression were examined while the concentration of H2O2 and HOCl level were determined. The effect of VPO1 RNA interference on cell proliferation, HOCl generation and ID1 expression were observed. The effect of NADPH oxidase inhibitor, diphenyleneiodonium (DPI), hydrogen peroxide scavenger, catalase and VPO1 inhibitor, 4-aminobenzoic acid hydrazide (ABAH) on VPO1 expression and the proliferation activity of PASMCs were observed. Moreover, the direct effects of HOCl on ID1 expression were also examined.
Results In cultured PASMCs, treatment with hypoxia significantly increased the proliferation activity while up-regulated VPO1, ID1 expression and generation of HOCl. Using VPO1 RNA interference PASMCs, effects of hypoxia on HOCl generation, ID1 expression were significantly inhibited. Pretreatment with DPI, catalase and ABAH also inhibit hypoxia-mediated cell proliferation and up-regulation of VPO1, ID1 expression and HOCl generation. Furthermore, treatment with HOCl also markedly increased the ID1 expression.
Conclusions These results indicate that VPO1 is involved in pulmonary arterial hypertension by play a key role in the pulmonary arterial smooth cells proliferation via H2O2/VPO1/HOCl/ID1 pathway.