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Article

Vascular Endothelial Growth Factor and Angiogenesis

Laboratory of Experimental Oncology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium (A.H., B.L., A.T.V.O., E.A.D.B.); and Department of Cancer Medicine, Ninewells Hospital, Dundee, United Kingdom (M.S.H.)

Abstract

I. Introduction

II. Vascular Endothelial Growth Factor

A. The Locations and Structures of Vascular Endothelial Growth Factor

B. Vascular Endothelial Growth Factor Receptors

C. Signal Transduction

D. Regulation of Gene Expression

E. Physiological Regulation of Vascular Endothelial Growth Factor in Normal Adults

III. Vascular Endothelial Growth Factor in Tumor Growth

A. Vascular Endothelial Growth Factor and Tumorigenesis

B. Lymphangiogenesis and Tumor Growth

C. The Role of Vascular Endothelial Growth Factor in the Impaired Host Antitumor Immune Response

D. Vascular Endothelial Growth Factor as a Prognostic Factor or an Indicator of Angiogenesis

E. Potential Therapeutic Applications Related to Vascular Endothelial Growth Factor

IV. Vascular Endothelial Growth Factor in Nonmalignant Disease

A. Rheumatoid Arthritis and Osteoarthritis

B. Cardiovascular Ischemia

C. Peripheral Vascular Disease

D. Diabetes Mellitus

E. Endometriosis, Preeclampsia, and Ovarian Hyperstimulation Syndrome

F. Psoriatic Skin Disease

V. Conclusions and Future Directions

Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro- and antiangiogenic molecules have already been discovered. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF in physiological and pathological processes is reviewed. We also discuss how modulation of VEGF expression creates new therapeutic possibilities and describe recent developments in this field.

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