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Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells

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Abstract

Objective

The coxsackie and adenovirus receptor (CAR) mediates the entry of coxsackievirus B (CVB) and adenovirus into host cells and is, therefore, a key determinant for the molecular pathogenesis of viral diseases such as myocarditis. The aim was to investigate the influence of HMG-CoA reductase inhibitor lovastatin on CAR expression in endothelial cells.

Methods

Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of lovastatin (0.05–5 μmol/l) for up to 48 h. Alterations in CAR expression were examined by quantitative real-time PCR (qRT-PCR) and flow cytometry. In addition, after treatment with 1 μmol/l lovastatin for 48 h, HUVECs were infected for 8 h with CVB3 and virus replication was detected by qRT-PCR using viral-specific TaqMan probes.

Results

We found that lovastatin decreases CAR mRNA expression by up to 80 % (p < 0.01) and CAR protein expression by up to 19 % (p < 0.01), in a concentration-dependent manner. Moreover, virus replication of CVB3 was significantly inhibited after lovastatin treatment (p < 0.05). The signaling mechanism of CAR down-regulation by lovastatin depends on the Rac1/Cdc42 pathway.

Conclusion

This study shows for the first time that lovastatin reduces the expression of CAR and subsequently the replication of CVB3 in HUVECs.

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Acknowledgments

We thank Hendrik Milting (PhD) for facilitating Real-Time PCR and Heike Seidenstücker for supporting viral infection studies. We also very much appreciate funding of our research by the FoRUM programme of the Ruhr-University Bochum (grant F722-11), and a donation by the Symnick-Foundation, Bielefeld, Germany.

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Authors and Affiliations

  1. Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University of Bochum, Georgstr. 11, 32545, Bad Oeynhausen, NRW, Germany

    Bianca Werner, Sven Dittmann, Carsten Funke, Cornelia Piper, Dieter Horstkotte & Martin Farr

  2. Center for Biotechnology (CeBiTec), Bielefeld University, Universitätsstr. 27, 33615, Bielefeld, NRW, Germany

    Karsten Niehaus

  3. Department of Molecular and Medical Virology, Ruhr University of Bochum, Universitätsstr. 150, 44801, Bochum, NRW, Germany

    Klaus Überla

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  1. Bianca Werner
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Correspondence to Bianca Werner.

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Responsible Editor: Ikuo Morita.

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Werner, B., Dittmann, S., Funke, C. et al. Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells . Inflamm. Res. 63, 267–276 (2014). https://doi.org/10.1007/s00011-013-0695-z

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  • DOI: https://doi.org/10.1007/s00011-013-0695-z

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