Effect of 15-hydroperoxyeicosatetraenoic acid on the fibrinolytic factor release and the antithrombin binding of vascular endothelial cells.

Abstract

15-Hydroperoxyeicosatetraenoic acid (15-HPETE), an arachidonate lipoxygenase product, is reported to induce severe endothelial injury. In this study, we examined the effect of 15-HPETE on the release of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) from cultured human umbilical vein endothelial cells (HUVEC). The addition of 15-HPETE to the serum-free medium reduced the release of t-PA antigen from HUVEC, while the release of PAI-1 antigen was significantly enhanced. However, treatment of the cultured HUVEC with alpha-tocopherol or nordihydroguaiaretic acid completely suppressed the 15-HPETE-induced change in t-PA and PAI-1 antigen release. 15-Hydroxyeicosatetraenoic acid (15-HETE) had no effect on the release of either antigen from cultured HUVEC. The HUVEC surfaces exposed to 15-HPETE decreased the potency for binding antithrombin III. In a reconstituted system with heparin and phosphatidylcholine, 15-HPETE decreased the ability of heparin to inactivate thrombin activity. These results suggest that the fibrinolytic factor release and the antithrombin binding of vascular endothelial cells are impaired by the attack of 15-HPETE, and that the presence of antioxidants prevents the injurious action of lipid hydroperoxide.