Activation of human vascular endothelial cells by factor Xa: Effect of specific inhibitors

Recently, human umbilical vein endothelial cells (HUVEC) have been shown to express functional high-affinity receptors for factor Xa, which may be of importance in the regulation of coagulation and homeostasis of the vascular wall. In this paper, we demonstrate that when added to cultured HUVEC, fac tor Xa was a potent mitogen, stimulating an increase in cell number at a 0. 3 to 100 nM concentration. The same doses of factor Xa also increased intra cellular free calcium levels and phosphoinositide turnover. When added to c onfluent HUVEC, factor Xa induced the expression of tissue factor and the r elease of tissue-type plasminogen activator and plasminogen activator inhib itor-1 without affecting urokinase expression. Indirect (antithrombin-penta saccharide) and direct (DX9065) inhibitors of factor Xa affected all these activities of factor Xa in a dose-dependent manner. Taken together, these d ata show that the activities induced by factor Xa on HUVEC were dependent o n its catalytic activity and could be inhibited by both direct and indirect factor Xa inhibitors. (C) 1999 Elsevier Science Inc.