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(Circulation. 2004;109:532-536.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Hydroxymethyl-Glutaryl Coenzyme A Reductase Inhibition Limits Cytomegalovirus Infection in Human Endothelial Cells

Luciano Potena, MD^*; Giada Frascaroli, BS^*; Francesco Grigioni, MD; Tiziana Lazzarotto, BS; Gaia Magnani, MD, PhD; Luciana Tomasi, BS; Fabio Coccolo, MD; Liliana Gabrielli, MD; Carlo Magelli, MD; Maria P. Landini, MD; Angelo Branzi, MD

From the Institute of Cardiology (L.P., F.G., G.M., L.T., F.C., C.M, A.B.) and the Institute of Experimental Medicine, Section of Microbiology (G.F., T.L., L.G., M.P.L.), University of Bologna, Bologna, Italy; and the Department of Virology, Institute of Microbiology, Albert Einstein University, Ulm, Germany (G.F.).

Correspondence to Carlo Magelli, MD, Institute of Cardiology, Pad. 21, Via Massarenti 9, 40138 Bologna, Italy. E-mail bibcard{at}almadns.unibo.it; lpotena@cvmed.stanford.edu

Received March 4, 2003; de novo received July 31, 2003; revision received October 2, 2003; accepted October 6, 2003.

Background— Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells.

Methods and Results— Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 µmol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 µmol/L fluvastatin-treated cells than in infected controls (10.5±0.9 versus 0.34±0.03 per 10³ pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-B binding activity in CMV-infected cells.

Conclusions— HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-B binding activity.

Key Words: statins • atherosclerosis • endothelium • infection • viruses

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