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Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation

Official URL:https://doi.org/10.1161/01.CIR.0000083367.93022.78
PubMed:View item in PubMed
Creators Name:Dechend, R. and Gieffers, J. and Dietz, R. and Joerres, A. and Rupp, J. and Luft, F.C. and Maass, M.
Journal Title:Circulation
Journal Abbreviation:Circulation
Volume:108
Number:3
Page Range:261-265
Date:22 July 2003
Keywords:Statins, Chlamydia Pneumoniae, Atherosclerosis, Infection, Immunology, Animals, Mice
Abstract: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-{kappa}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-κB activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae-induced signaling and transmission.
ISSN:0009-7322
Publisher:American Heart Association (U.S.A.)
Item Type:Article

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