Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells

Bianca Werner1, Sven Dittmann, Carsten Funke

  • 1Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University of Bochum, Georgstr. 11, 32545, Bad Oeynhausen, NRW, Germany, bwerner@hdz-nrw.de.

Abstract

Insights

Lovastatin, a statin drug, reduces coxsackie and adenovirus receptor (CAR) expression in endothelial cells. This inhibition subsequently decreases coxsackie B virus 3 (CVB3) replication, offering potential therapeutic insights.

Area of Science:

  • Molecular biology
  • Virology
  • Cardiovascular research

Background:

  • The coxsackie and adenovirus receptor (CAR) is crucial for coxsackievirus B (CVB) and adenovirus entry into host cells.
  • CAR plays a key role in the molecular pathogenesis of viral diseases, including myocarditis.

Purpose of the Study:

  • To investigate the effect of HMG-CoA reductase inhibitor, lovastatin, on CAR expression in endothelial cells.
  • To determine if lovastatin influences CVB3 replication in human umbilical vein endothelial cells (HUVECs).

Main Methods:

  • HUVECs were treated with varying concentrations of lovastatin (0.05-5 μmol/l) for up to 48 hours.
  • CAR expression was quantified using quantitative real-time PCR (qRT-PCR) and flow cytometry.
  • CVB3 replication was assessed via qRT-PCR in lovastatin-treated HUVECs.

Main Results:

  • Lovastatin significantly decreased CAR mRNA expression by up to 80% and CAR protein expression by up to 19% in a dose-dependent manner.
  • Lovastatin treatment resulted in significant inhibition of CVB3 replication.
  • The mechanism involves lovastatin-induced down-regulation of CAR via the Rac1/Cdc42 pathway.

Conclusions:

  • Lovastatin reduces CAR expression in HUVECs.
  • Lovastatin inhibits CVB3 replication in HUVECs, suggesting a potential therapeutic strategy for viral myocarditis.

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