MAINTENANCE AND REPAIR OF VASCULAR ENDOTHELIUM

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Our specific aims are: 1) To further characterize brain and pituitary fibroblast growth factors (FGF) already purified by FPLC, by determining their primary structure. The relationship between brain and pituitary FGF will also be determined using monoclonal antibodies developed against both molecules. Their relationship with the endothelial cell growth factor (ECGF) will be determined. 2) The interaction of bovine brain and pituitary FGF with cultured endothelial cells originating from various vascular territories and species will be determined and the FGF receptors characterized. 3) The effect in vitro of FGF on endothelial cell migration, as well as its possible role as a chemotactic agent in vitro will be determined. 4) Finally, using monoclonal antibodies agaist FGF, its distribution in various tissues, neoplasms, or cultured cells known to contain angiogenic factors in vivo will be eq. determined. The angiogenic activity of FGF in three different in vivo models (rabbit cornea, Hamster pouch, and chick chorioallantoid membrane) will be analyzed as well as the ability of FGF antibodies to block such activity in vivo. The factor(s) in basement membranes (BM) which mimics the effect of FGF will be determined. The effect of FGF on the synthesis and integration of such factors in the BM synthesized by cultured vascular endothelial cells will be analyzed. The effect of both BM and FGF on the maintenance and turnover of the transferrin receptor which is required for endothelial cells to divide, and which in vivo (erythropoietic system), or in organ culture (metanephric mesenchyme), has been shown to be inducible and to correlate with the appearance of specific BM components will be analyzed.