VASCULAR ENDOTHELIAL GROWTH-FACTOR, PLATELET-DERIVED GROWTH-FACTOR, AND INSULIN-LIKE GROWTH-FACTOR-I PROMOTE RAT AORTIC ANGIOGENESIS IN-VITRO

The purpose of this study was to evaluate the vasoformative response o f isolated vascular explants to a variety of growth factors that have been shown to stimulate angiogenesis. Rings of rat aorta were cultured in collagen gels under serum-free conditions in the presence or absen ce of vascular endothelial growth factor (VEGF), natural platelet-deri ved growth factor (PDGF), PDGF-AA, PDGF-BB, insulin-like growth factor -1 (IGF-1), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), epidermal growth factor (EGF), int erleukin-1 alpha (IL-1 alpha), or hepatocyte growth factor (HGF). The angiogenic response of the rat aorta was stimulated by VEGF, PDGF, PDG F-AA, PDGF-BB, and IGF-1. Maximum stimulatory effects were obtained wi th VEGF and PDGF-BB. By contrast, TGF-beta 1 and IL-1 alpha had inhibi tory activity. No significant effects were observed with TGF-alpha, EG F, or HGF. The vascular outgrowth of VEGF-stimulated cultures was prim arily composed of microvessels, whereas that of PDGF- and IGF-1-stimul ated cultures contained an increased number of fibroblast-like cells. The inability of TGF-alpha, TGF-beta 1, IL-1 alpha, EGF, and HGF to st imulate rat aortic angiogenesis in serum-free culture suggests that ei ther these factors require the mediatory activity of accessory cells t hat are not present in the rat aorta model or that blood vessels are h eterogeneous in their capacity to respond to different angiogenic fact ors.