Heparin-binding growth factor-I (endothelial cell growth factor) binds to endothelium in vivo

Heparin-binding growth factor-I (HBGF-I) produces a significant increase in endothelial cell replication in vitro and may prove useful for endothelial regeneration and endothelial seeding in vivo. Heparin enhances the mitogenic effects of HBGF-I in vitro and may be an important adjunct to its pharmacologic use. Binding studies in the rat were undertaken to determine the feasibility of use of HBGF-I in vivo. For saturation studies, 125I-labeled HBGF-I was administered intravenously at various concentrations with heparin (approximately 5 U/ml blood volume). Further binding studies were conducted with the use of a constant concentration of 125I-labeled HBGF-I (40 ng) with or without heparin (2.5 U/ng HBGF-I). In each case, the rat was perfused with ice-cold saline solution 5 minutes after drug administration and the aorta or carotid arteries were harvested. 125I-labeled HBGF-I with heparin demonstrated saturation binding to rat aortic endothelium at an approximate blood concentration of 10 ng/ml. Scatchard plot analysis of in vivo data revealed a binding constant (KD) of 1.60 +/- 0.004 x 10(-9) mol/L compared with 2 to 8 x 10(-10) mol/L obtained for in vitro binding. Receptor number per cell was approximately 3000 for rat aortic endothelium, compared with a receptor number of 2000 to 20,000 for several endothelial cell lines, including bovine aortic endothelial cells, determined in vitro. 125I-labeled HBGF-I binding to uninjured rat carotid endothelium was significantly increased (p = 0.0001) by heparin (463 +/- 302 cpm to 1172 +/- 403 cpm).(ABSTRACT TRUNCATED AT 250 WORDS)