The modulation of heparin-like activity of endothelial cells in experimental systems.

Anticoagulantly active heparin-like glycosaminoglycans are apparently present on the vascular surface. We have tried to modulate heparin-like substances on endothelial cells using an experimental cell culture system. Perturbation of the endothelial proteoglycan metabolism by beta-D-xyloside resulted in a reduced biosynthesis of cell surface heparan sulfate, and impaired antithrombin III binding to endothelial cells in parallel with an inhibition of endothelial cell heparin-like activity. In a separate series of experiments, treatments of endothelial cells with interleukin 1 beta and tumor necrosis factor alpha, physiological mediators of immunologic and inflammatory responses, were shown to cause an inhibition of the synthesis of endothelial cell surface heparan sulfate. The endothelial heparin-like activity was partially diminished by these cytokines, suggesting that cytokine-mediated suppression of heparin-like substance on endothelial cells is another cytokine-inducible endothelial effect affecting coagulation. The modulation of endothelial heparin-like activity by these pharmacological and physiological agents may have pathophysiological implications in thrombosis.