Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Vascular Medicine
Urotensin II Stimulates Vascular Endothelial Growth Factor Secretion From Adventitial Fibroblasts in Synergy With Angiotensin II
Nana SongWenhui DingSongyun ChuJing ZhaoXiao DongBeibing DiChaoshu Tang
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JOURNAL FREE ACCESS

2012 Volume 76 Issue 5 Pages 1267-1273

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Abstract

Background: The adventitia plays an important role in and is considered to be the initiating site for vascular remodeling. Urotensin II (UII) and angiotensin II (Ang II) are the two most important vascular peptides involved in vascular remodeling in the adventitia. Nevertheless, little is known about their effect on the expression of vascular endothelial growth factor (VEGF). It was hypothesized that both UII and Ang II could induce VEGF expression in adventitial fibroblasts and VEGF may play a role in cell proliferation and collagen I synthesis induced by UII or Ang II. Methods and Results: Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII and/or Ang II and inhibitors of the mitogen-activated protein kinase (MAPK) pathway or VEGF-neutralizing antibodies. The VEGF expression was evaluated using enzyme-linked immunosorbent assay (ELISA), while the proliferation and collagen I synthesis were detected using methyl thiazol tetrazolium (MTT) assay and ELISA. It was found that: (1) both UII and Ang II could stimulate VEGF expression in adventitial fibroblasts and they had a synergistic effect; (2) MAPK pathway inhibitors could inhibit VEGF secretion induced by UII and/or Ang II; and (3) VEGF-neutralizing antibodies could inhibit UII/Ang II-induced cell proliferation and collagen synthesis in adventitial fibroblasts. Conclusions: Induction of VEGF expression may be a new mechanism involved in vascular remodeling for UII and Ang II. (Circ J 2012; 76: 1267-1273)

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© 2012 THE JAPANESE CIRCULATION SOCIETY
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