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The Biology of Vascular Endothelial Growth Factor

Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080

I. Introduction

II. Biological Activities of VEGF

III. Organization of the VEGF Gene

IV. Properties of the VEGF Isoforms

V. Regulation of VEGF Gene Expression

A. Hypoxia

B. Cytokines

C. Differentiation and transformation

VI. The VEGF Receptors

A. Characterization and distribution of VEGF-binding sites

B. The Flt-1 and Flk-1/KDR tyrosine kinases

1. Binding characteristics

2. Signal transduction

3. Regulation

4. Structural requirements for ligand binding in Flt-1 and Flk-1/KDR

5. VEGF determinants for binding Flt-1 and Flk-1/KDR

VII. VEGF-Related Molecules

VIII. Role of VEGF and Its Receptors in Physiological Angiogenesis

A. Distribution of VEGF, Flk-1/KDR and Flt-1 mRNA

B. Analysis of Flk-1/KDR, Flt-1 and VEGF gene knockouts

IX. Role of VEGF in Pathological Angiogenesis

A. Tumor angiogenesis

1. Expression of VEGF in human tumors

2. Inhibition of VEGF action in vivo

B. Intraocular neovascular syndromes

C. Other pathological conditions

X. Therapeutic Applications of VEGF-Induced Angiogenesis

XI. Perspectives