Journal of Pharmacological Sciences | |
Demeanor of rivaroxaban in activated/inactivated FXa | |
Toku Sakashita1  Jun Tanno1  Takaaki Senbonmatsu1  Kaname Seki1  Toshihiro Muramatsu1  Shintaro Nakano1  Shigeyuki Nishimura1  Yosuke Mizuno2  Yasushi Okazaki2  | |
[1] Department of Cardiology, Saitama Medical University, International Medical Center, Saitama, Japan;Division of Functional Genomics & Systems Medicine, Saitama Medical University Research Center for Genomic Medicine, Saitama, Japan; | |
关键词: Activated factor X; Anticoagulant; Inflammation; Rivaroxaban; Gene modulation; | |
DOI : 10.1016/j.jphs.2017.02.010 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown