Abstract
Several cytokine families have roles in the development, maintenance, and remodeling of the microcirculation. Of these, the vascular endothelial growth factor (VEGF) family is one of the best studied and one of the most complex. Five VEGF ligand genes and five cell-surface receptor genes are known in the human, and each of these may be transcribed as multiple splice isoforms to generate an extensive family of proteins, many of which are subject to further proteolytic processing. Using the VEGF family as an example, we describe the current knowledge of growth-factor expression, processing, and transport in vivo. Experimental studies and computational simulations are being used to measure and predict the activity of these molecules, and we describe avenues of research that seek to fill the remaining gaps in our understanding of VEGF family behavior.
Acknowledgements
The authors gratefully acknowledge constructive discussions with Brian Annex, David Bates, Margaret Brown, Patricia D'Amore, David Ginty, Olga Hudlicka, Alex Kolodkin, Christopher Kontos, Gera Neufeld, Shay Soker, and Hiroshi Takagi. The authors’ work on the VEGF family was supported by National Institutes of Health (NIH; Bethesda, Maryland, USA) grants HL079653 and HL087351. FMG was supported by NIH training grant T32 HL7284 through the Robert M. Berne Cardiovascular Center.