Role Of Vascular Peroxidase1in Vascular Remodeling In Pulmonary Arterial Hypertension

Chapter I Relationship between vascular peroxidase concentration in serum and pulmonary artery hypertensionObjectivePulmonary arterial hypertension(PAH) are a class of clinical disease characterized by elevated pulmonary artery pressure. The close relationship between oxidative stress and PAH was confirmed by numerous research. Vascular peroxidase(VPO), which including VPOl and VPO2at least, is a new member of Heme-containing peroxidase family. VPOl and VPO2both can catalyze H2O2(weak oxidant)to generate HOCl(strong oxidant) to enhance the effect of oxidative stress, while VPO expressed in vascular tissue mainly as VPOl. Based on the important role of oxidative stree played in the pathogenesis of PAH and the promoting oxidative stree ability of VPOl, this researchwe was aimed to investigate the relationship between VPOl serum level and PAH.MethodsBlood sample was taken from59PAH patient and43Chinese healthy subjects. Plasma level of VPOl was assayed by Western Blot; Plasma level of H2O2was assayed by ELISA. Relationship between VPO1, H2O2and pulmonary artery pressure were analyzed.ResultsSerum VPO1level was significantly higher in PAH patients(127.46±7.47ng/μl) than healthy subjects(89.94±7.91ng/μl), while there was no gender difference of VPO1level.ConclusionThe serum level of VPO1has a relationship with PAH. Chapter II Involvement of vascular peroxidasel in proliferation of rat pulmonary arterial smooth cellsObjectiveHypoxia could induce pulmonary arterial smooth muscle cells (PASMCs) proliferation via hydrogen peroxide(H2O2)-induced oxidative stress and inhibitor of differentiationl (idl) was also involved. Earlier research had demonstrated that vascular peroxidase1(VPOl) could catalyze the reaction of H2O2and chloride to produce hypochlorous acid(HOCl). This study was aimed to determine the potential role of VPO1in proliferation of PASMCs during pulmonary arterial hypertension. MethodsPrimary rat PASMCs were extracted and treated with hypoxia(3%O2). Proliferation activity of PASMCs, VPO1and idl expression, H2O2and HOCl level were examined. The effect of diphenyleneiodonium(DPI), catalase and4-aminobenzoic acid hydrazide (ABAH) on VPO1expression and the proliferation activity of PASMCs were observed. The effect of VPOl siRNA on hypoxia-induced cell proliferation was also observed.ResultHypoxia induced proliferation of PASMCs, while DP1, catalase and ABAH could attenuate the effect of hypoxia treatment. Moreover, DPI, catalase and ABAH could also inhibit hypoxia-mediated up-regulation of VPO1, HOCl and idl. Interference of VPO1with VPOl siRNA significantly inhibited the proliferation activity of PASMCs and the increased levels of HOCl and idl by hypoxia treatment.ConclusionHypoxia treatment could increase expression of VPO1and induce PASMCs proliferation by oxidative stress signal of Nox/H2O2/VPOl/HOCl/idl.