Heparin affinity of anionic and cationic capillary endothelial cell growth factors: analysis of hypothalamus-derived growth factors and fibroblast growth factors

Abstract

Bovine hypothalamus-derived growth factors (HDGF), pituitary fibroblast growth factor (FGF), and brain FGF were analyzed by chromatography on immobilized heparin and tested for the ability to stimulate the proliferation of capillary endothelial (CE) cells. Two distinct CE cell growth factors were found in hypothalamus, one anionic (aHDGF; pI of about 5) and one cationic (cHDGF; pI of about 8). Both aHDGF and cHDGF adhered tightly to immobilized heparin. They were eluted with 0.9-1.1 M NaCl and 1.3-1.5 M NaCl, respectively. Pituitary and brain FGF were also found to bind to immobilized heparin and to stimulate CE cell proliferation. Pituitary FGF was eluted at 1.4-1.6 M NaCl. The elution profile of brain FGF showed that two peaks of CE cell growth factor activity were eluted from the heparin column, one at 1.0 M NaCl and a second at 1.4-1.6 M NaCl. The tight binding of all of these growth factors to heparin (particularly aHDGF, whose binding is unexpected because of its negative charge) is presented as evidence that CE cell growth factors all share an affinity for heparin.