Molecular mechanism of VEGF and its role in pathological angiogenesis

J Cell Biochem. 2022 Dec;123(12):1938-1965. doi: 10.1002/jcb.30344. Epub 2022 Oct 26.

Abstract

Over the last seven decades, a significant scientific contribution took place in the delineation of the implications of vascular endothelial-derived growth factor (VEGF) in the processes of angiogenesis. Under pathological conditions, mainly in response to hypoxia or ischemia, elevated VEGF levels promote vascular damage and the growth of abnormal blood vessels. Indeed, the development of VEGF biology has revolutionized our understanding of its role in pathological conditions. Hence, targeting VEGF or VEGF-mediated molecular pathways could be an excellent therapeutic strategy for managing cancers and intraocular neovascular disorders. Although anti-VEGF therapies, such as monoclonal antibodies and small-molecule tyrosine kinase inhibitors, have limited clinical efficacy, they can still significantly improve the overall survival rate. This thus demands further investigation through the development of alternative strategies in the management of VEGF-mediated pathological angiogenesis. This review article focuses on the recent developments toward the delineation of the functional biology of VEGF and the role of anti-VEGF strategies in the management of tumor and eye pathologies. Moreover, therapeutic angiogenesis, an exciting frontier for the treatment of ischemic disorders, is highlighted in this review, including wound healing.

Keywords: VEGF; angiogenesis; cancer; eye diseases; hypoxia.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Humans
  • Neoplasms* / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factors / metabolism
  • Vascular Endothelial Growth Factors / therapeutic use
  • Wound Healing

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Angiogenesis Inhibitors