Protein family review

This in an extract of a protein family review which first appeared in GenomeBiology, and is reproduced by permission of the publisher, BioMedCentral Ltd.

Authors:

David IR Holmes1 ,2 and Ian Zachary1

1BHF Laboratories and The Rayne Institute, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
2Ark Therapeutics Ltd, 1 Fitzroy Mews, London W1T 6DE, UK

Correspondence:

Ian Zachary

Email:

I.Zachary@ucl.ac.uk

Read the full article

Subscribers to GenomeBiology may view the full version of this review article online at http://genomebiology.com/2005/6/2/209

Published:

1 February 2005

The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease

Summary

Vascular endothelial growth factors (VEGFs) are a family of secreted polypeptides with a highly conserved receptor-binding cystine-knot structure similar to that of the platelet-derived growth factors. VEGF-A, the founding member of the family, is highly conserved between animals as evolutionarily distant as fish and mammals. In vertebrates, VEGFs act through a family of cognate receptor kinases in endothelial cells to stimulate blood-vessel formation. VEGF-A has important roles in mammalian vascular development and in diseases involving abnormal growth of blood vessels; other VEGFs are also involved in the development of lymphatic vessels and disease-related angiogenesis. Invertebrate homologs of VEGFs and VEGF receptors have been identified in fly, nematode and jellyfish, where they function in developmental cell migration and neurogenesis. The existence of VEGF-like molecules and their receptors in simple invertebrates without a vascular system indicates that this family of growth factors emerged at a very early stage in the evolution of multicellular organisms to mediate primordial developmental functions.

Frontiers

Although significant progress has been made towards elucidating the mechanisms mediating the angiogenic effects of VEGF-A, several formidable challenges lie ahead. The biological and signaling roles of the VEGF receptors, particularly VEGFR1 and neuropilin-1, have not yet been fully defined. Another key goal is the identification of the mechanisms underlying the role of VEGF-A in endothelial cell differentiation and early vascular development. An emergent area of interest is the study of VEGF and VEGFR homologs in invertebrates. A better understanding of how VEGF ligand-receptor systems function in Drosophila and C. elegans will shed light on the ancestral function of this family of molecules and may also generate novel insights into their biological roles in vertebrates. Another major goal in the future will be to clarify the distinct biological functions of different members of the VEGF family.

A key area of ongoing research will be the role of VEGFs in human disease. As recent work on ALS demonstrates [48,49], it is likely that new insights into the importance of VEGFs for disease will continue to be generated. Consequently, the scope for using anti-VEGF approaches therapeutically will grow, and the challenge will be to develop more effective and economic ways to prevent VEGF-driven pathophysiological angiogenesis or to correct VEGF deficits. The future use of VEGF therapy for cardiovascular disease remains an enticing prospect but awaits confirmatory data from clinical studies.

Comparison of human VEGFs with PDGFs and related sequences from Drosophila and Orf virus

Gene organization and encoded functional domains of the human VEGF genes and related genes from Drosophila