Heparin enhances endothelial cell von Willebrand factor content by growth factor dependent mechanisms

Von Willebrand factor (vWf), a multimeric adhesive glycoprotein synthesized, stored, and secreted in megakaryocytes and endothelial cells, is normally found in plasma, platelets and subendothelium. While many substances mediate the release of vWf from endothelial cells, factors that enhance vWf synthesis and partitioning to its regulated pathway are currently unknown. We studied the effect of pharmacologic doses of heparin on the vWf content of endothelial cells. After a lag of 8 h and in the presence of crude or purified growth factor, heparin at doses between 0.25 and 2 U (1.4-11 micrograms)/ml, increased the content of high molecular weight vWf. The increased amounts of vWf were localized to Weibel-Palade bodies and extracellular matrix. Lower molecular weight highly sulfated heparin or heparin-like compounds were most active in growth factor dependent endothelial cell vWf expression. There was no clear importance of polysaccharide sequence or protein core.