Demeanor of rivaroxaban in activated/inactivated FXa

Activated factor x (fxa) plays an important role in thrombin generation and inflammation. factor x is not converted constitutively to fxa,but only after intrinsic clotting factors are activated and/or cellular injury occurs. although rivaroxaban is one of direct fxa inhibitors,its function in the inactivated coagulation cascade is unclear. in human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2,high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in dna microarray. upon fxa stimulation,the expressions of pro-inflammatory genes such as monocyte chemoattractant protein-1 (mcp-1),intracellular adhesion molecule-1,and interleukin-8 were maximally increased at 4 h after stimulation,and were suppressed by rivaroxaban. to confirm these results,quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (elisa) for mcp-1 were performed. fxa evoked the expression of mcp-1 maximally at 4 h after stimulation,whereas mcp-1 displayed a different temporal activation in elisa. interestingly,rivaroxaban inhibited both time courses of mcp-1 expression. these results suggest that rivaroxaban may not influence gene modulation in the inactivated coagulation state,but can attenuate the endothelial damage evoked by fxa and pro-inflammatory cytokine genes. © 2017 the authors