VEGF Signaling Pathway

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VEGF Pathway Overview

Vascular endothelial growth factor (VEGF) is a major regulator of new blood vessel growth and an important inducer of vascular permeability. VEGF is the founding member of a family of homodimeric glycoproteins that are structurally related to the platelet-derived growth factors (PDGF). This VEGF family of proteins binds selectively with different affinities to at least five distinct receptors (VEGFRs) (1).

A variety of physiological and pathological processes are associated with up-regulation of components of the VEGF/VEGFR-system, including embryogenesis, the female reproductive cycle, pregnancy, wound healing, tumor growth, diabetic retinopathy and ischemic diseases. While VEGF is required for blood vessel formation during embryogenesis, upregulation of VEGF in response to tumor hypoxia stimulates pathological angiogenesis that allows tumor growth.  In contrast, enhanced expression of VEGF under hypoxic conditions has a protective effect on neurons, neural stem cells, and glial cells such as astrocytes or Schwann cells (2).

Anti-VEGF therapy has many advances in the treatment of certain cancers and intraocular neovascular disorders. Further characterization of the VEGF signaling effects is critical for better understanding of whether VEGF itself or its inhibitors, can be used to treat diseases without negatively affecting other cell types in the body, including the novel concept of VEGF as adjuvant therapy to stem cell transplantation, in patients with heart failure (3 and 4).

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References

1. VEGF receptor signal transduction.
2. Vascular endothelial growth factor (VEGF) inhibition--a critical review.
3. Ten years of anti-vascular endothelial growth factor therapy.
4. Vascular endothelial growth factor in heart failure.