1. Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation.
- Author
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Shi R, Hu C, Yuan Q, Yang T, Peng J, Li Y, Bai Y, Cao Z, Cheng G, and Zhang G
- Subjects
- Analysis of Variance, Animals, Aorta, Thoracic enzymology, Aorta, Thoracic pathology, Cells, Cultured, Disease Models, Animal, Enzyme Activation, Enzyme Inhibitors pharmacology, Extracellular Matrix Proteins genetics, Free Radical Scavengers pharmacology, Hydrogen Peroxide metabolism, Hypertension pathology, Hypochlorous Acid metabolism, Male, Mesenteric Arteries enzymology, Mesenteric Arteries pathology, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 metabolism, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle pathology, NADPH Oxidases antagonists & inhibitors, NADPH Oxidases metabolism, Peroxidase genetics, RNA Interference, RNA, Messenger metabolism, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Signal Transduction, Time Factors, Peroxidasin, Angiotensin II metabolism, Cell Proliferation drug effects, Extracellular Matrix Proteins metabolism, Hypertension enzymology, Muscle, Smooth, Vascular enzymology, Myocytes, Smooth Muscle enzymology, Peroxidase metabolism
- Abstract
Aims: Vascular peroxidase 1 (VPO1) is a newly identified haem-containing peroxidase that catalyses the oxidation of a variety of substrates by hydrogen peroxide (H(2)O(2)). Considering the well-defined effects of H(2)O(2) on the vascular remodelling during hypertension, and that VPO1 can utilize H(2)O(2) 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., Methods and Results: 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., Conclusion: VPO1 is a novel regulator of vascular smooth muscle cell proliferation via NADPH oxidase-H(2)O(2)-VPO1-hypochlorous acid-ERK1/2 pathways, which may contribute to vascular remodelling in hypertension.
- Published
- 2011
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