Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR- and - receptors

A newly discovered PDGF isoform, PDGF-CC, is expressed in actively angiogenic tissues such as placenta, some embryonic tissues, and tumors. We test the possibility that PDGF-CC promotes angiogenesis in vivo. The core domain (mature form) of human PDGF-CC is sufficiently potent to stimulate neovascularization in the mouse cornea. The corneal angiogenic response induced by PDGF-CC is robust although the area of neovascularization is smaller than those of FGF-2and VEGF-stimulated angiogenesis. Similarly, PDGF-BB and PDGF-AB induce angiogenic responses virtually indistinguishable from PDGF-CCstimulated vessels. In contrast, PDGF-AA displays only a weak angiogenic response in the mouse cornea. Although there was no significant difference in incorporation of mural cells to the newly formed blood vessels induced by PDGF-BB and -CC, the percentage of mural cell positive vessels induced by PDGF-AA was greater than those induced by FGF-2, PDGF-BB, and PDGF-CC. In the developing chick embryo, PDGF-CC induced branch sprouts from established blood vessels. In PDGF receptor-transfected endothelial cells, PDGF-CC activated the PDGF receptor alpha subunit (PDGFR). PDGF-CC, but not PDGF-AA, was able to activate PDGFRreceptor in endothelial cells that coexpress both and forms of receptors. Thus, the PDGF-CC-mediated angiogenic response is most likely transduced by PDGFand receptors. These data demonstrate that the PDGF family is a complex and important group of proangiogenic factors.—Cao, R., Bråkenhielm, E., Li, X., Pietras, K., Widenfalk, J, Östman, A., Eriksson, U., Cao, Y. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFRand receptors. FASEB J. 16, 1575–1583 (2002)