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(Circulation. 2004;110:2283-2286.)
© 2004 American Heart Association, Inc.

Editorial

The Role of Vascular Endothelial Growth Factor in Restenosis

The Controversy Continues

Ichiro Shiojima, MD, PhD; Kenneth Walsh, PhD

From the Department of Cardiovascular Science and Medicine, Chiba University School of Medicine, Chiba, Japan (I.S.), and the Department of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass (K.W.).

Correspondence to Kenneth Walsh, PhD, Boston University School of Medicine, Molecular Cardiology/CVI, 700 Albany St, W611, Boston, MA 02118-2526. E-mail kxwalsh@bu.edu

Key Words: Editorials • angiogenesis • restenosis • endothelium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 1996, the late Jeffrey Isner proposed the use of vascular endothelial growth factor (VEGF) gene delivery in patients undergoing percutaneous transluminal angioplasty as a strategy to limit the risk of restenosis.¹VEGF promotes endothelial cell function and is a potent stimulator of endothelial cell migration and survival. Because normal endothelium inhibits smooth muscle cell proliferation, it was hypothesized that accelerating the reendothelialization of the balloon-injured site would diminish the severity of restenosis. Indeed, reports in animal models demonstrate that local administration of VEGF-A or VEGF-C leads to accelerated reendothelialization and a reduction in intimal thickening.^2–5

However, the utility of VEGF or other proangiogenic factors for the treatment of restenosis is questioned by reports that have documented extensive vascular networks in atherosclerotic plaques⁶ and balloon-injured coronary arteries.⁷ Thus, the delivery of proangiogenic agents might exacerbate the growth of vascular lesions, analogous to the concept that angiogenesis contributes to tumor growth. These concerns are supported by studies showing that treatment of apolipoprotein E (ApoE)-deficient mice with an angiogenesis inhibitor reduced intimal neovascularization and plaque growth,⁸ and administration of VEGF enhanced atherosclerotic plaque progression, which was associated with increased capillary density.⁹

See pp 2424, 2430, 2436, 2444

This controversy has been rekindled by 3 articles appearing in the present issue of Circulation.^10–12 Although many of the previous studies focused on the effects of exogenously administered angiogenic growth factors on vascular lesions, these new studies analyze the role of endogenous angiogenic growth factor signaling in neointima formation after acute vascular injury. . . . [Full Text of this Article]

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Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury

Randolph Hutter, Francine E. Carrick, Carolina Valdiviezo, Claire Wolinsky, John S. Rudge, Stanley J. Wiegand, Valentin Fuster, Juan J. Badimon, and Bernhard V. Sauter
Circulation 2004 110: 2430-2435. [Abstract] [Full Text]

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

Kisho Ohtani, Kensuke Egashira, Ken-ichi Hiasa, Qingwei Zhao, Shiro Kitamoto, Minako Ishibashi, Makoto Usui, Shujiro Inoue, Yoshikazu Yonemitsu, Katsuo Sueishi, Masataka Sata, Masabumi Shibuya, and Kenji Sunagawa
Circulation 2004 110: 2444-2452. [Abstract] [Full Text]

Angiogenesis-Dependent and Independent Phases of Intimal Hyperplasia

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Circulation 2004 110: 2436-2443. [Abstract] [Full Text]

Adenoviral Gene Transfer With Soluble Vascular Endothelial Growth Factor Receptors Impairs Angiogenesis and Perfusion in a Murine Model of Hindlimb Ischemia

Johannes Jacobi, Betty Y.Y. Tam, Grace Wu, Jana Hoffman, John P. Cooke, and Calvin J. Kuo
Circulation 2004 110: 2424-2429. [Abstract] [Full Text]

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