PMID- 28314697
OWN - NLM
STAT- MEDLINE
DCOM- 20170801
LR  - 20190816
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 133
IP  - 3
DP  - 2017 Mar
TI  - Demeanor of rivaroxaban in activated/inactivated FXa.
PG  - 156-161
LID - S1347-8613(17)30025-7 [pii]
LID - 10.1016/j.jphs.2017.02.010 [doi]
AB  - 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.
CI  - Copyright (c) 2017 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Seki, Kaname
AU  - Seki K
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Mizuno, Yosuke
AU  - Mizuno Y
AD  - Division of Functional Genomics & Systems Medicine, Saitama Medical University 
      Research Center for Genomic Medicine, Saitama, Japan.
FAU - Sakashita, Toku
AU  - Sakashita T
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Nakano, Shintaro
AU  - Nakano S
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Tanno, Jun
AU  - Tanno J
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Okazaki, Yasushi
AU  - Okazaki Y
AD  - Division of Functional Genomics & Systems Medicine, Saitama Medical University 
      Research Center for Genomic Medicine, Saitama, Japan.
FAU - Muramatsu, Toshihiro
AU  - Muramatsu T
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Nishimura, Shigeyuki
AU  - Nishimura S
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan.
FAU - Senbonmatsu, Takaaki
AU  - Senbonmatsu T
AD  - Department of Cardiology, Saitama Medical University, International Medical 
      Center, Saitama, Japan; Research Administration Center, Saitama Medical 
      University, Saitama, Japan. Electronic address: senbont@saitama-med.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170224
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Proteinase-Activated)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9NDF7JZ4M3 (Rivaroxaban)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Factor Xa/*pharmacology
MH  - Factor Xa Inhibitors/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Interleukin-8/genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, Proteinase-Activated/genetics
MH  - Rivaroxaban/*pharmacology
OTO - NOTNLM
OT  - Activated factor X
OT  - Anticoagulant
OT  - Gene modulation
OT  - Inflammation
OT  - Rivaroxaban
EDAT- 2017/03/21 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/03/19 06:00
PHST- 2016/11/02 00:00 [received]
PHST- 2017/01/24 00:00 [revised]
PHST- 2017/02/17 00:00 [accepted]
PHST- 2017/03/21 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/03/19 06:00 [entrez]
AID - S1347-8613(17)30025-7 [pii]
AID - 10.1016/j.jphs.2017.02.010 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2017 Mar;133(3):156-161. doi: 10.1016/j.jphs.2017.02.010. Epub 
      2017 Feb 24.