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(Circulation. 2003;108:261.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Hydroxymethylglutaryl Coenzyme A Reductase Inhibition Reduces Chlamydia pneumoniae-Induced Cell Interaction and Activation

Ralf Dechend, MD; Jens Gieffers, MD; Rainer Dietz, MD; Achim Joerres, MD; Jan Rupp, MD; Friedrich C. Luft, MD; Matthias Maass, MD

From Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, HELIOS Klinikum-Berlin (R. Dechend, R. Dietz, F.C.L.); the Department of Nephrology and Medical Intensive Care, Virchow Campus, Medical Faculty of the Charité, Humboldt University of Berlin, Germany (A.J.); and the Department of Medical Microbiology and Hygiene, University of Lubeck, Germany (J.G., J.R., M.M.).

Correspondence to Ralf Dechend, MD, Franz Volhard Clinic, Wiltberg Strasse 50, 13125 Berlin, Germany. E-mail dechend{at}fvk-berlin.de

Received August 20, 2002; de novo received April 8, 2003; revision received June 9, 2003; accepted June 9, 2003.

Background— Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms.

Methods and Results— We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by 33%. Western blotting made it apparent that VSMC infection resulted in increased cell membrane-associated RhoA and Rac1, implying increased prenylation of these proteins. This effect was blocked by statin but circumvented by mevalonate. Cytochrome C assays showed that infected VSMCs produced increased reactive oxygen species that was blocked by statin. Infection increased nuclear transcription factor-B expression in VSMCs that was dose-dependently suppressed by statin. Infected VSMCs produced and released RANTES and MCP-1. Statin dose-dependently blocked this production both at the mRNA and protein levels. Mevalonate and M geranylgeranylpyrophosphate circumvented these effects.

Conclusions— C pneumoniae can be transmitted from macrophages to VSMCs. VSMCs showed an activation profile typical of atherosclerosis, namely Rac1 and RhoA prenylation, nuclear transcription factor-B activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae-induced signaling and transmission.

Key Words: statins • Chlamydia pneumoniae • atherosclerosis • infection • immunology

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