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.
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 hypertensiverats 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 hypertensiverats. 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: S Baldus; J P Eiserich; A Mani; L Castro; M Figueroa; P Chumley; W Ma; A Tousson; C R White; D C Bullard; M L Brennan; A J Lusis; K P Moore; B A Freeman Journal: J Clin Invest Date: 2001-12 Impact factor: 14.808
Authors: M L Brennan; M M Anderson; D M Shih; X D Qu; X Wang; A C Mehta; L L Lim; W Shi; S L Hazen; J S Jacob; J R Crowley; J W Heinecke; A J Lusis Journal: J Clin Invest Date: 2001-02 Impact factor: 14.808
Authors: Jimin Guo; Hui Chen; Joanne Ho; Johanna Mancini; Thomas Sontag; Stéphane A Laporte; Darren E Richard; Jean-Jacques Lebrun Journal: Cell Signal Date: 2009-06 Impact factor: 4.315
Authors: Gautam Bhave; Christopher F Cummings; Roberto M Vanacore; Chino Kumagai-Cresse; Isi A Ero-Tolliver; Mohamed Rafi; Jeong-Suk Kang; Vadim Pedchenko; Liselotte I Fessler; John H Fessler; Billy G Hudson Journal: Nat Chem Biol Date: 2012-07-29 Impact factor: 15.040