PMID- 10630515
OWN - NLM
STAT- MEDLINE
DCOM- 20000201
LR  - 20190721
IS  - 0163-2116 (Print)
IS  - 0163-2116 (Linking)
VI  - 44
IP  - 12
DP  - 1999 Dec
TI  - A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte 
      chemoattractant protein-1 expression after ischemia-reperfusion injury in rat 
      liver.
PG  - 2568-76
AB  - Activated factor X (FXa) is a trypsinlike serine protease involved in the cascade 
      of blood coagulation. The monocyte chemoattractant protein-1 (MCP-1) may be 
      important in the pathophysiology of liver ischemia-reperfusion injury. We 
      investigated the effects of a selective FXa inhibitor, DX-9065a, on MCP-1 
      expression after ischemia-reperfusion in the rat liver. Liver ischemia was 
      induced in rats by occluding the portal vein for 30 min. DX-9065a was injected 
      intravenously 5 min before vascular clamping. Serum concentrations of MCP-1 were 
      measured by enzyme-linked immunosorbent assay. The levels of MCP-1 mRNA in the 
      liver after reperfusion were determined by northern blot analysis. In vitro MCP-1 
      production by peritoneal macrophages in response to alpha-thrombin was examined. 
      Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. 
      However, pretreatment of animals with DX-9065a resulted in significantly smaller 
      increases in the serum concentration of MCP-1 after reperfusion in a 
      dose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 
      mRNA levels in the liver after ischemia-reperfusion. In vitro MCP-1 production by 
      peritoneal macrophages was enhanced by alpha-thrombin. In addition, DX-9065a 
      significantly reduced tissue factor mRNA levels in peripheral monocytes after 
      ischemia-reperfusion, compared to untreated animals. In conclusion, a selective 
      inhibitor of FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion 
      of the rat liver.
FAU - Yamaguchi, Y
AU  - Yamaguchi Y
AD  - Department of Surgery II, Kumamoto University Medical School, Japan.
FAU - Okabe, K
AU  - Okabe K
FAU - Liang, J
AU  - Liang J
FAU - Matsumura, F
AU  - Matsumura F
FAU - Ohshiro, H
AU  - Ohshiro H
FAU - Ishihara, K
AU  - Ishihara K
FAU - Matsuda, T
AU  - Matsuda T
FAU - Takeya, M
AU  - Takeya M
FAU - Kuratsu, J I
AU  - Kuratsu JI
FAU - Mori, K
AU  - Mori K
FAU - Yamada, S
AU  - Yamada S
FAU - Ogawa, M
AU  - Ogawa M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 
      ((2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic 
      acid)
RN  - 0 (Anticoagulants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Naphthalenes)
RN  - 0 (Propionates)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - Chemokine CCL2/*blood
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Factor Xa Inhibitors
MH  - Kupffer Cells/metabolism
MH  - Liver/*blood supply/chemistry
MH  - Macrophages, Peritoneal/metabolism
MH  - Male
MH  - Naphthalenes/*pharmacology
MH  - Propionates/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/*blood
EDAT- 2000/01/12 00:00
MHDA- 2000/01/12 00:01
CRDT- 2000/01/12 00:00
PHST- 2000/01/12 00:00 [pubmed]
PHST- 2000/01/12 00:01 [medline]
PHST- 2000/01/12 00:00 [entrez]
AID - 10.1023/a:1026667912632 [doi]
PST - ppublish
SO  - Dig Dis Sci. 1999 Dec;44(12):2568-76. doi: 10.1023/a:1026667912632.