ISSN:
1573-2568
Keywords:
FACTOR XA INHIBITOR
;
MONOCYTE CHEMOATTRACTANT PROTEIN-1
;
REPERFUSION INJURY
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Activated factor X (FXa) is a trypsinlike serineprotease involved in the cascade of blood coagulation.The monocyte chemoattractant protein-1 (MCP-1) may beimportant in the pathophysiology of liverischemia-reperfusion injury. We investigated the effects of aselective FXa inhibitor, DX-9065a, on MCP-1 expressionafter ischemia-reperfusion in the rat liver. Liverischemia was induced in rats by occluding the portalvein for 30 min. DX-9065a was injected intravenously5 min before vascular clamping. Serum concentrations ofMCP-1 were measured by enzyme-linked immunosorbentassay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blotanalysis. In vitro MCP-1 production by peritonealmacrophages 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 insignificantly smaller increases in the serumconcentration of MCP-1 after reperfusion in adose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNAlevels in the liver after ischemia-reperfusion. In vitroMCP-1 production by peritoneal macrophages was enhancedby alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheralmonocytes after ischemiareperfusion, compared tountreated animals. In conclusion, a selective inhibitorof FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the ratliver.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1026667912632
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