ScienceVEGF

VEGF: the predominant regulator of angiogenesis

Among the many factors implicated in angiogenesis, VEGF has been identified as the most potent and predominant. The scope of scientific research involving VEGF continues to grow exponentially. From 1995–2005, the number of VEGF-related abstracts presented at the annual meeting of ASCO increased 50-fold, highlighting the increased focus in research upon the role of VEGF in oncology.

 

What is VEGF?

VEGF (also known as VEGF-A, but commonly referred to simply as VEGF) stands for 'vascular endothelial growth factor'. This protein plays an important role in angiogenesis. As its name suggests, VEGF stimulates vascular endothelial cell growth, survival and proliferation. As seen in preclinical models, VEGF has been shown to facilitate survival of existing vessels, contribute to vascular abnormalities that may impede effective delivery of antitumour compounds, and stimulate new vessel growth.^3,4,6–9

 

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The structure of VEGF

This ribbon representation shows a dimerised VEGF/VEGFR complex, as observed by X-ray crystallography. Two monomers of VEGF (blue and yellow) are shown bound to domain two of the VEGFR-1 receptor (green).³ Ferrara N. Vascular endothelial growth factor: basic science and clinical progress.

 

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The VEGF family of proteins

VEGF is a member of a family of six structurally related proteins (see table) that regulate the growth and differentiation of multiple components of the vascular system, especially blood and lymph vessels. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2.^3,4

 

There are four major isotypes of VEGF-A (VEGF), each coded for by a different portion of the VEGF gene. These isotypes are VEGF₁₂₁, VEGF₁₆₅, VEGF₁₈₉, and VEGF₂₀₆.^10–13 Although these isotypes behave identically in solution, they differ in their ability to bind heparin and the extracellular matrix.¹⁴