Published Online
on July 19, 2004

A more recent version of this article appeared on September 1, 2004

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Submitted on April 15, 2004
Revised on May 4, 2004

Essential Role of Vascular Endothelial Growth Factor in Angiotensin II-Induced Vascular Inflammation and Remodeling

Qingwei Zhao; Minako Ishibashi; Ken-ichi Hiasa; Chunyan Tan; Akira Takeshita; and Kensuke Egashira^*

From the Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

^* To whom correspondence should be addressed. E-mail: egashira{at}cardiol.med.kyushu-u.ac.jp.

Abstract--Angiotensin II (Ang II) upregulates vascular endothelial growth factor (VEGF) and activates vascular inflammation. However, the decisive role of VEGF in Ang II-induced vascular inflammation and remodeling has not been addressed. Ang II infusion to wild-type mice increased local expression of VEGF and its receptors in cells of aortic wall and plasma VEGF, and caused aortic inflammation (monocyte infiltration) and remodeling (wall thickening and fibrosis). Hypoxia-inducible factor-1 colocalized with VEGF-positive cell types. Blockade of VEGF by the soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated the Ang II-induced inflammation and remodeling. The sFlt-1 gene transfer also inhibited the increased expression of VEGF and inflammatory factors such as monocyte chemoattractant protein-1. In contrast, sFlt-1 gene transfer did not affect Ang II-induced arterial hypertension and cardiac hypertrophy. VEGF is an essential mediator in Ang II-induced vascular inflammation and structural changes through its proinflammatory actions.

Key words: growth substances • arteriosclerosis • remodeling • angiotensin II • endothelial growth factors

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