title: Atorvastatin inhibits functional expression of proatherogenic TLR2 in arterial endothelial cells.
abstract: BACKGROUND
  There is growing evidence that TLR2 plays a role in the pathogenesis of atherosclerosis. It is highly expressed in endothelial cells in areas of disturbed blood flow, like plaques or vessel bifurcations, but laminar blood flow suppresses endothelial TLR2 expression and is therefore thought to be atheroprotective. We sought for means to also protect lesion prone sites from TLR2 over-expression and subsequent endothelial activation.
  
  
  METHODS
  Human coronary artery endothelial cells (HCAEC) were treated with atorvastatin (ATV) and TLR2 surface expression was determined by FACS analyses. Western blot analyses were used to explore the phosphorylation status of SP1.
  
  
  RESULTS
  ATV profoundly inhibited basal and stimulated endothelial TLR2 expression in a time- and dose-dependent manner. It also inhibited HCAEC activation by MALP-2. TLR2 surface expression was inversely correlated to SP1 serine phosphorylation and was casein kinase 2 dependent.
  
  
  CONCLUSIONS
  We demonstrate that ATV can control over-expression of proinflammatory endothelial TLR2 protein and TLR2-mediated endothelial activation. The mechanism involves casein kinase 2 and SP1 phosphorylation. ATV effects on endothelial cell TLR2 are comparable to those of laminar blood flow and might therefore also be atheroprotective.
authors.affiliation: Department of Internal Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, Austria.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bertocchi
authors.forename: Michaela
authors.initials: M
authors.lastname: Traunwieser
authors.forename: Jakob
authors.initials: J
authors.lastname: Dörler
authors.forename: Julia
authors.initials: J
authors.lastname: Hasslacher
authors.forename: Michael
authors.initials: M
authors.lastname: Joannidis
authors.forename: Stefan
authors.initials: S
authors.lastname: Dunzendorfer
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D047390:Casein Kinase II / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006325:Heart Atria / Q000166:cytology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides / Q000378:metabolism; D010766:Phosphorylation; D011758:Pyrroles / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D055666:Lipopeptides; D011758:Pyrroles; D016329:Sp1 Transcription Factor; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D000069059:Atorvastatin; C106335:macrophage stimulatory lipopeptide 2; D047390:Casein Kinase II