Published Online
on October 11, 2004

A more recent version of this article appeared on October 19, 2004

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Submitted on June 18, 2004
Revised on August 14, 2004
Accepted on August 20, 2004

Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells

Kisho Ohtani MD, Kensuke Egashira MD, PhD^*, Ken-ichi Hiasa MD, Qingwei Zhao MD, Shiro Kitamoto MD, Minako Ishibashi MD, Makoto Usui MD, Shujiro Inoue MD, Yoshikazu Yonemitsu MD, Katsuo Sueishi MD, Masataka Sata MD, Masabumi Shibuya MD, and Kenji Sunagawa MD

From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.

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

Background--Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed.

Methods and Results--We report herein that blockade of VEGF by soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. sFlt-1 gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation.

Conclusions--Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells.

Key words: restenosis • remodeling • inflammation • endothelium-derived factors • gene therapy

Related Article:

The Role of Vascular Endothelial Growth Factor in Restenosis: The Controversy Continues

Ichiro Shiojima and Kenneth Walsh
Circulation 2004 110: 2283-2286. [Extract] [Full Text]

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