Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation.

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.

• Authors: Ruizheng Shi, Changping Hu, Qiong Yuan, Tianlun Yang, Jun Peng, Yuanjian Li, Yongping Bai, Zehong Cao, Guangjie Cheng, Guogang Zhang
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 91 Issue 1 Pg. 27-36 (Jul 01 2011) ISSN: 1755-3245 [Electronic] England
• PMID: 21292788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Extracellular Matrix Proteins
• Free Radical Scavengers
• RNA, Messenger
• Angiotensin II
• Hypochlorous Acid
• Hydrogen Peroxide
• peroxidasin
• Peroxidase
• NADPH Oxidases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Analysis of Variance
• Angiotensin II (metabolism)
• Animals
• Aorta, Thoracic (enzymology, pathology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Extracellular Matrix Proteins (genetics, metabolism)
• Free Radical Scavengers (pharmacology)
• Hydrogen Peroxide (metabolism)
• Hypertension (enzymology, pathology)
• Hypochlorous Acid (metabolism)
• Male
• Mesenteric Arteries (enzymology, pathology)
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Muscle, Smooth, Vascular (drug effects, enzymology, pathology)
• Myocytes, Smooth Muscle (drug effects, enzymology, pathology)
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Peroxidase (genetics, metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Signal Transduction
• Time Factors