title: Simvastatin blunts endotoxin-induced tissue factor in vivo.
abstract: 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.
  
  
  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.
authors.affiliation: Second Department of Medicine, Division of Angiology, Medical University of Vienna,Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Walter S
authors.initials: WS
authors.lastname: Speidl
authors.forename: Johannes
authors.initials: J
authors.lastname: Pleiner
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Zorn
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Erich
authors.initials: E
authors.lastname: Minar
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D004731:Endotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D015539:Platelet Activation / Q000187:drug effects; D011292:Premedication; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D019851:Thrombophilia / Q000139:chemically induced / Q000188:drug therapy; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013925:Thromboplastin; D019821:Simvastatin