PMID- 24624928
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20211021
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 13
DP  - 2014 Mar 13
TI  - Advanced glycation end products potentiate citrated plasma-evoked oxidative and 
      inflammatory reactions in endothelial cells by up-regulating protease-activated 
      receptor-1 expression.
PG  - 60
LID - 10.1186/1475-2840-13-60 [doi]
AB  - Advanced glycation end products (AGEs) and receptor RAGE interaction contribute 
      to endothelial cell damage in diabetes. Several thrombogenic abnormalities are 
      also involved in diabetic vascular complications. However, the pathological role 
      of thrombin and protease-activated receptor-1 (PAR-1) system in AGE-induced 
      endothelial cell (EC) damage remains unclear. In this study, we investigated the 
      effects of rivaroxaban, an inhibitor of factor Xa on 3% citrated human 
      plasma-evoked reactive oxygen species (ROS) generation and RAGE, monocyte 
      chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) 
      gene expression in AGE-exposed ECs. We further examined whether FR171113, an 
      inhibitor of PAR-1 blocked the plasma-induced EC damage and if AGEs increased 
      PAR-1 expression in ECs. Human citrated plasma stimulated ROS generation and 
      RAGE, MCP-1 and ICAM-1 expression in ECs, all of which were potentiated by the 
      treatment with AGEs. Rivaroxaban or FR171113 significantly inhibited these 
      derangements in plasma- or plasma plus AGE-exposed ECs. Moreover, AGEs 
      significantly increased the PAR-1 levels in ECs. The present study suggests that 
      citrated plasma could induce oxidative and inflammatory reactions in ECs via the 
      activation of thrombin-PAR-1 system and that AGEs could potentiate the 
      plasma-evoked EC damages via up-regulation of PAR-1. Blockade of the crosstalk 
      between AGE-RAGE axis and coagulation system by rivaroxaban might be a novel 
      therapeutic target for thromboembolic disorders in diabetes.
FAU - Ishibashi, Yuji
AU  - Ishibashi Y
FAU - Matsui, Takanori
AU  - Matsui T
FAU - Ueda, Seiji
AU  - Ueda S
FAU - Fukami, Kei
AU  - Fukami K
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
AD  - Department of Pathophysiology and Therapeutics of Diabetic Vascular 
      Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 
      830-0011, Japan. shoichi@med.kurume-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140313
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Benzamides)
RN  - 0 (FR 171113)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (Thiazolidines)
RN  - 2968PHW8QP (Citric Acid)
SB  - IM
MH  - Benzamides/pharmacology
MH  - Citric Acid/metabolism/pharmacology
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Gene Expression Regulation
MH  - Glycation End Products, Advanced/*metabolism
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Oxidative Stress/drug effects/*physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor, PAR-1/*biosynthesis
MH  - Thiazolidines/pharmacology
MH  - Up-Regulation/drug effects/*physiology
PMC - PMC3995632
EDAT- 2014/03/15 06:00
MHDA- 2014/11/02 06:00
PMCR- 2014/03/13
CRDT- 2014/03/15 06:00
PHST- 2013/12/12 00:00 [received]
PHST- 2014/03/08 00:00 [accepted]
PHST- 2014/03/15 06:00 [entrez]
PHST- 2014/03/15 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
PHST- 2014/03/13 00:00 [pmc-release]
AID - 1475-2840-13-60 [pii]
AID - 10.1186/1475-2840-13-60 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2014 Mar 13;13:60. doi: 10.1186/1475-2840-13-60.