RGD Reference Report - A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.

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A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.
Authors:	Yamaguchi, Y Okabe, K Liang, J Matsumura, F Ohshiro, H Ishihara, K Matsuda, T Takeya, M Kuratsu, J I Mori, K Yamada, S Ogawa, M
Citation:	Yamaguchi Y, etal., Dig Dis Sci. 1999 Dec;44(12):2568-76. doi: 10.1023/a:1026667912632.
RGD ID:	14995929
Pubmed:	PMID:10630515 (View Abstract at PubMed)
DOI:	DOI:10.1023/a:1026667912632 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
CCL2	Human	Liver Reperfusion Injury	treatment	ISO	Ccl2 (Rattus norvegicus)		RGD
Ccl2	Rat	Liver Reperfusion Injury	treatment	IEP			RGD
Ccl2	Mouse	Liver Reperfusion Injury	treatment	ISO	Ccl2 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Mus musculus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Homo sapiens)

CCL2 (C-C motif chemokine ligand 2)

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A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.