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document
Simvastatin blunts endotoxin-induced tissue factor in vivo . BACKGROUND Beyond lipid lowering , various antiinflammatory properties have been ascribed to statins . Moreover , in vitro studies have suggested the presence of anticoagulant effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors , as lipopolysaccharide ( LPS ) -induced monocyte tissue factor ( TF ) was suppressed . In this study , we examined the role of statins in experimental endotoxemia on inflammatory and procoagulant responses in vivo . METHODS AND RESULTS In this double-blind , placebo-controlled , parallel-group study , 20 healthy , male subjects were randomized to receive either simvastatin ( 80 mg/d ) or placebo for 4 days before intravenous administration of LPS ( 20 IU/kg IV ) . Plasma high-sensitive C-reactive protein ( hsCRP ) , monocyte chemoattractant protein ( MCP-1 ) , sCD40L , sCD40 , and prothrombin fragment F1+2 ( F1.2 ) were determined by ELISAs at baseline and at 4 and 8 hours after LPS administration . Monocyte TF expression and monocyte-platelet aggregates were measured by whole-blood flow cytometry over the same time course . The increases in hsCRP and MCP-1 , both known inducers of TF , were significantly suppressed by statin treatment after LPS challenge . Statin premedication blunted the increase of monocyte TF expression in response to LPS . In parallel , endotoxin-induced formation of F1.2 was significantly reduced by simvastatin after 4 and 8 hours . LPS infusion affected neither the formation and activation of monocyte-platelet aggregates nor plasma levels of sCD40 and sCD40L . CONCLUSIONS Simvastatin suppresses the inflammatory response to endotoxin and blunts monocyte TF expression but does not affect platelet activation .
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Intervention_Pharmacological
Simvastatin
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Intervention_Pharmacological
statins
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
simvastatin
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Intervention_Control
placebo
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Intervention_Pharmacological
Statin
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Intervention_Pharmacological
simvastatin
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Intervention_Pharmacological
Simvastatin
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Outcome_Physical
Plasma high-sensitive C-reactive protein ( hsCRP )
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Outcome_Physical
monocyte chemoattractant protein ( MCP-1 )
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Outcome_Physical
sCD40L , sCD40
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Outcome_Physical
prothrombin fragment F1+2 ( F1.2 )
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Outcome_Physical
Monocyte TF expression and monocyte-platelet aggregates
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Outcome_Physical
hsCRP
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Outcome_Physical
MCP-1
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Outcome_Physical
monocyte TF expression
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Outcome_Physical
formation of F1.2
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Outcome_Physical
formation and activation of monocyte-platelet aggregates
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Outcome_Physical
plasma levels of sCD40 and sCD40L
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Outcome_Physical
monocyte TF expression
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Outcome_Physical
platelet activation
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Participant_Condition
endotoxemia
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Participant_Sample-size
20
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Participant_Condition
healthy
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Participant_Sex
male