title: Involvement of vascular peroxidase 1 in angiotensin II-induced hypertrophy of H9c2 cells.
abstract: Oxidative stress has been implicated in cardiac hypertrophy and heart failure. Vascular peroxidase 1 (VPO1), a peroxidase in the cardiovascular system, uses the hydrogen peroxide (H2O2) derived from co-expressed NADPH oxidases (NOX) to produce hypochlorous acid (HOCl) and catalyze peroxidative reactions. Our previous studies showed that VPO1 contributes to the vascular smooth muscle cell proliferation and endothelial dysfunction in spontaneous hypertensive rats (SHRs); however, the role of VPO1 in cardiomyocytes hypertrophy is still uninvestigated. The present study was therefore undertaken to examine the role of VPO1 in the angiotensin II-induced cardiac hypertrophy, and the underlying mechanism by which VPO1 regulates the redox signaling. As compared to WKY rats, the SHRs exhibited increased myocyte cross sectional area, enhanced Nox2 and VPO1 expression level in cardiac tissue, and an increased Ang II level in plasma. In cultured H9c2 cell line, Ang II increased the hypertrophy-related gene (BNP/ANF) expression and the cellular surface area, which was attenuated by knocking down of VPO1 via VPO1 siRNA or pharmacological inhibition of NOX/VPO1 pathway. Moreover, the enhanced hypochlorous acid (HOCl) production and phosphorylation of ERK1/2 was suppressed by VPO1 knockdown. Furthermore, the protective role of VPO1 siRNA transfection on H9c2 cardiomyocytes hypertrophy was abrogated on the HOCl stimulation, and the phosphorylated ERK1/2 expression level was found also upregulated after HOCl stimulation. In conclusion, these results suggest that the Nox2/VPO1/HOCl/ERK1/2 redox signaling pathway was implicated in the pathogenesis of Ang II-induced cardiac hypertrophy.
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhaoya
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zaixin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xysrz2010@sina.com.
authors.forename: Ruizheng
authors.initials: R
authors.lastname: Shi
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D055785:Gene Knockdown Techniques; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000473:pathology*; D006984:Hypertrophy / Q000473:pathology; D006997:Hypochlorous Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D000074662:NADPH Oxidase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D001713:Biphenyl Compounds; D006420:Hemeproteins; D009861:Onium Compounds; D034741:RNA, Small Interfering; C031291:diphenyliodonium; D000804:Angiotensin II; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; C573339:vascular peroxidase, rat; D010544:Peroxidases; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Angiotensin II; VPO1 (vascular peroxidase 1); cardiac hypertrophy