Low molecular weight heparin enhances prostacyclin production by cultured human endothelial cells

Confluent cultures of vascular endothelial cells derived from the human umbilical vein were incubated in a serum-free medium in the presence of low molecular weight heparin (LMWH) with molecular weights of 4000-6000 dalton (Da), or of unfractionated heparin (UFH) with average molecular weight 12,000 Da, and prostacyclin production was determined by radioimmunoassay for 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. LMWH at 1 U/ml as anti-factor Xa activity significantly increased prostacyclin production after 6h or longer; however, UFH at 1 USP U/ml did not induce such a significant change. The LMWH-induced increase in prostacyclin production occurred at 0.1 U/ml and above after 6 h of treatment. Since prostacyclin is both a potent inhibitor of platelet aggregation and a vasodilator, it was suggested that the increased endothelial cell prostacyclin production induced by LMWH may be a component of the anticoagulant activity of the drug.