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STATE-OF-THE-ART PAPER

Vascular Endothelial Growth Factors

Biology and Current Status of Clinical Applications in Cardiovascular Medicine

Seppo Ylä-Herttuala, MD, PhDFESC^_*,,,_*, Tuomas T. Rissanen, MD, PhD^_*, Ismo Vajanto, MD and Juha Hartikainen, MD, PhD

^_* Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, Kuopio University
Department of Medicine
Department of Surgery, Kuopio University and Kuopio University Hospital
Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

Manuscript received April 17, 2006; revised manuscript received September 22, 2006, accepted September 27, 2006.

^_* Address for correspondence: Dr. Seppo Ylä-Herttuala, Professor of Molecular Medicine, Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. (Email: seppo.ylaherttuala{at}uku.fi).

Members of the vascular endothelial growth factor (VEGF) family are among the most powerful modulators of vascular biology. They regulate vasculogenesis, angiogenesis, and vascular maintenance during embryogenesis and in adults. Because of their profound effects on blood vessels, VEGFs have received much attention regarding their potential therapeutic use in cardiovascular medicine, especially for therapeutic vascular growth in myocardial and peripheral ischemia. However, completed randomized controlled VEGF trials have not provided convincing evidence of clinical efficacy. On the other hand, recent preclinical proangiogenic VEGF studies have given insight, and anti-VEGF studies have shown that the disturbance of vascular homeostasis by blocking VEGF-A may lead to endothelial dysfunction and adverse vascular effects. Excess VEGF-A may contribute to neovascularization of atherosclerotic lesions but, currently, there is no evidence that transient overexpression by gene transfer could lead to plaque destabilization. Here, we review the biology and effects of VEGFs as well as the current status of clinical applications and future perspectives of the therapeutic use of VEGFs in cardiovascular medicine.

Abbreviations and Acronyms   CAD = coronary artery disease   CCS = Canadian Cardiovascular Society   CLI = critical limb ischemia   EC = endothelial cell   NO = nitric oxide   PAD = peripheral arterial disease   PlGF = placental growth factor   pu = particle units   SMC = smooth muscle cell   VEGF = vascular endothelial growth factor   VEGFR = VEGF receptor

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