625 Original Paper Cell Physiol Biochem 2011;28:625-630 Accepted: September 12, 2011 Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Biochemistr and Biochemistr and Biochemistr and Biochemistr and Biochemistry Copyright © 2011 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2011 S. Karger AG, Basel 1015-8987/11/0284-0625$38.00/0 Accessible online at: www.karger.com/cpb Atorvastatin Inhibits Functional Expression of Proatherogenic TLR2 in Arterial Endothelial Cells Cristina Bertocchi a,1 , Michaela Traunwieser a,3 , Jakob Dörler 2 , Julia Hasslacher 1 , Michael Joannidis 1 and Stefan Dunzendorfer 1 1 Medical University of Innsbruck, Department of Internal Medicine, Innsbruck, 2 Medical University of Innsbruck, Department of Cardiology, Innsbruck, 3 Kantonsspital Graubuenden, Department of Gynecology, Chur, a contributed equally Stefan Dunzendorfer Department of Internal Medicine, Medical University of Innsbruck Anichstrasse 35, 6020 Innsbruck (Austria) Tel. +43-512-50481302, Fax +43-512-50424199 E-Mail stefan.dunzendorfer@i-med.ac.at 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 bifurca- tions, but laminar blood flow suppresses endothelial TLR2 expression and is therefore thought to be atheroprotective. We sought for means to also pro- tect 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 sur- face expression was determined by FACS analyses. Western blot analyses were used to explore the phos- phorylation status of SP1. Results: ATV profoundly inhibited basal and stimulated endothelial TLR2 ex- pression 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 de- pendent. Conclusion: We demonstrate that ATV can control over-expression of proinflammatory endothe- lial 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. Key Words Toll-like receptors  Atherosclerosis  Statins  Inflam- mation Introduction Atherosclerosis represents the major cause of mor- bidity and mortality in Western society [1]. Epidemiologic evidence has demonstrated a relationship between mi- crobial infection and disease, with experimental studies suggesting a causal role [2]. The inflammatory nature of this disease process is widely accepted; however, the pre- cise components of the atherogenic pro-inflammatory cascade remain controversial [3]. TLRs as principal sen- sors of the innate immune system provide a mechanistic link between infection, inflammation, and atherosclerosis [4]. Additionally, the possibility of endogenous ligand ac- tivation of TLRs might provide sterile inflammation links to atherosclerosis susceptibility [5]. To date, 10 TLRs have been described in humans with TLR1-9 conserved between the human and the mouse. These pattern recognition receptors have been