Heparin-endothelial cell interactions.
Recent observations have revealed that heparin influences endothelial cell proliferation in a number of ways unrelated to its anticoagulant properties. A majority of the nonanticoagulant actions of heparin on the endothelium appear to be related to heparin interactions with the fibroblast growth factors (FGFs). Members of this family of potent endothelial mitogens and angiogenic factors have been shown to bind with high affinity to immobilized heparin. It was this characteristic of the FGFs that initially allowed their purification to homogeneity. Subsequently, it has been shown that a unique characteristic of the FGFs is their lack of a signal sequence which results in their not being secreted by conventional means. However, both in vitro and in vivo studies have revealed that a significant proportion of the cell-synthesized FGF is found outside the cells, localized in the extracellular matrix bound to heparin-like glycosaminoglycans. These findings have led to the suggestion that matrix-associated FGF represents an extracellular reservoir that may be released by the action of heparan sulfate degrading enzymes introduced during inflammation or tumor metastasis or by heparin that is released from mast cells. We have recently shown that intravenous infusion of heparin into rabbits results in an increase in plasma levels of an FGF-like molecule. Other studies, in which investigators have infused FGF into normal normal animals, have revealed no effect of the circulating FGF on cells of a normal adult vasculature. However, release of FGF into the circulation, where there has been 'compromise' in the vascular system, indicate a dramatic influence on the rate of proliferation of vascular cells at the injured sites.
D'Amore
P A
PA
Children's Hospital, Boston, Mass.
D000818:Animals; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans
D016228:Endothelial Growth Factors; D005346:Fibroblast Growth Factors; D006493:Heparin