Sulfated polysaccharides modulate effects of acidic and basic fibroblast growth factors on repair of injured confluent human vascular endothelium.

Abstract

Semi-automatic analysis of the repair process of a circular mechanical lesion of confluent human vascular endothelial cells in vitro was used to evaluate the contributions of cell migration and cell proliferation. Standard heparin added to culture medium that contained 30% human serum induced an inhibition of cell migration at the lesion margin during the first day after injury. Several sulfated polysaccharides were tested in the presence of 5% human serum. Standard heparin, low molecular weight heparin, or pentosan polysulfate markedly reduced the rate of lesion regeneration. Cell proliferation, measured by 3H-thymidine incorporation at the lesion margin, and cell migration were both decreased. In contrast, the combination of acidic fibroblast growth factor with a sulfated polysaccharide accelerated the repair process. Basic fibroblast growth factor combined with a sulfated polysaccharide gave a regeneration rate similar to that of the control; however, at 4 days after injury, the residual lesion was the same when basic fibroblast growth factor was used alone or when it was combined with sulfated polysaccharides. Acidic fibroblast growth factor totally reversed the effects of sulfated polysaccharides on the repair process by enhancing endothelial cell proliferation and allowing endothelial cell migration.