Vascular Endothelial Growth Factor

VEGF and its functions have been described in many excellent reviews (7-10). It is a specific mitogen of endothelial cells and has been described as having at least five isoforms (7,8). A number of receptors for VEGF have been described including two specific tyrosine-kinase receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/fk-1) (7,8). VEGF stimulates endothelial cell proliferation and differentiation, increases vascular permeability, endothelium-dependent vasodilatation via NO, and plays a central role in physiological and pathological angiogenesis as well as modulating leukocyte migration (6,8). The importance of VEGF in angiogenesis is critical as deletion of the gene in mice results in major vascular defects and intrauterine death (11). In fact, topical application of VEGF improves wound healing by stimulating growth factors and by mobilizing cells, which contribute to new vessel formation (12). In addition, VEGF has been shown to promote tumor angiogenesis with clinical trials of agents, which block VEGF dependent pathways currently underway (7,8). VEGF has also been shown to play a role in hematopoiesis and hematological malignancies (8).

The importance of VEGF in the pathogenesis of proliferative diabetic retinopathy has been extensively examined. This role of VEGF has been substantiated in both animal (13-15) and human studies (16,17) and has recently been reviewed (18).

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