Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Abstract

Thrombin stimulates prostacyclin formation in cultured human endothelial cells. However, a countervailing process that prevents prostacyclin overproduction has not been described previously. In this study, we demonstrate that Factor Xa can inhibit prostacyclin synthesis induced by thrombin or sodium arachidonate. The required concentration of Factor Xa represents activation of only 2% of the Factor X in plasma. The inhibition is reversed by a human monoclonal antibody directed against the light chain of Factor Va (Mr = 78,000), which suggests that Factor Va is required for this down-regulation of prostacyclin production. Confluent human endothelial cells (10(7)) contained 1.4 to 2.2 micrograms of Factor V antigen as measured by a competitive enzyme-linked immunosorbent assay. The results indicate that in endothelial cells Factor Xa may play a regulatory role in prostacyclin formation through interaction with Factor Va.

Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator.

“…The levels of HUVE cell Factor V antigen obtained by our radioimmunoassay (-100 ng/106 cells) are comparable with that obtained using a competitive enzyme-linked immunosorbent assay, -1.2 ug/ I07 cells (41). If it is assumed that Factor V has a specific activity of 82 U/mg (24), the radioimmunoassay data would suggest that a 35-mm petri dish of HUVE cells has 8 mU of Factor V coagulant activity.…”

Expression of factor V on human umbilical vein endothelial cells is modulated by cell injury.

“…The apparent discrepancies between our study and the studies of Rodgers and Shuman, 20 Sinha et al, 22 and Maruyama et al 34 necessitate a close examination of all four studies. Indirect evidence for the presence of Factor V on the surface of bovine aortic and human umbilical vein endothelium in the functional studies of Rodgers and Shuman and Sinha et al and our inability to demonstrate Factor V by binding studies can be explained by the greater sensitivity of the functional studies through amplification by product formation.…”

“…Two studies have been concerned directly with the presence and role of Factor V in the regulation of coagulation by HUVEC. Sinha et al 22 from our laboratory recently reported that cultured human umbilical vein endothelial cells contained, but did not secrete, Factor V into the medium. They found that 200 molecules of Factor Xa bound to each endothelial cell in a monolayer resulted in the downregulation of production of PGI 2 .…”

“…The synthesis and release of Factor V by bovine aortic cells was shown by Cerveny et al 21 Unlike bovine endothelial cells, human endothelial cells from umbilical veins fail to secrete Factor V into the medium. 22 -M Thus, there is no extracellular source for Factor V.…”

“…In contrast, HUVEC synthesizes Factor V but fails to secrete it into the medium. 22 ' a In this paper, we report that although human Factor V a binds to HUVEC, it is not expressed on intact adherent cells. In contrast, injury to HUVEC can cause expression or exposure of Factor Va activity, presumably on the cell surface.…”