Demeanor of rivaroxaban in activated/inactivated FXa

• Main Authors: Kaname Seki (Author), Yosuke Mizuno (Author), Toku Sakashita (Author), Shintaro Nakano (Author), Jun Tanno (Author), Yasushi Okazaki (Author), Toshihiro Muramatsu (Author), Shigeyuki Nishimura (Author), Takaaki Senbonmatsu (Author)
• Format: Book
• Published: Elsevier, 2017-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1347-8613
10.1016/j.jphs.2017.02.010