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Effect of Simvastatin on MMPs and TIMPs in Human Brain Endothelial Cells and Experimental Stroke

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Abstract

Clinical studies demonstrated favorable effects of statins in stroke beyond lipid-lowering effects. In acute stroke, the disruption of the blood–brain barrier (BBB) is mediated by matrix metalloproteinases (MMPs). A modified MMP metabolism may account for the beneficial effects of statins. Cultured human brain microvascular endothelial cells (BMECs) were pretreated with simvastatin and subjected to oxygen glucose deprivation (OGD). Gene expression and protein secretion of MMP-2 and MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Simvastatin significantly dampened the expression but not secretion of MMP-2 under OGD. MMP-9 synthesis rate was low and unaffected by simvastatin treatment, while the gene expression and protein secretion of TIMP-1 and TIMP-2 were both strongly induced. Our results provide evidence for a positive effect of simvastatin on the MMP metabolism in human BMECs and experimental stroke mainly by means of the increased expression and secretion of TIMP-1 and TIMP-2.

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Acknowledgments

This study received a grant (contract grant number FP7/2007-2013) by the European Union’s Seventh Framework Programme under grant agreements 201024 and 202213 (European Stroke Network).

Conflict of Interest

Björn Reuter, Claus Rodemer, Saskia Grudzenski, Stephen Meairs, Michael G. Hennerici, and Marc Fatar declare that they have no conflict of interest

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Author notes

  1. Björn Reuter

    Present address: Department of Neurology, University Hospital of Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany

Authors and Affiliations

  1. Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Björn Reuter, Claus Rodemer, Saskia Grudzenski, Stephen Meairs, Michael G. Hennerici & Marc Fatar

  2. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, German Red Cross Blood Service Baden-Wuerttemberg–Hesse, Heidelberg University, Mannheim, Germany

    Peter Bugert

Authors
  1. Björn Reuter
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  2. Claus Rodemer
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  3. Saskia Grudzenski
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  4. Stephen Meairs
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  5. Peter Bugert
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  6. Michael G. Hennerici
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  7. Marc Fatar
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Correspondence to Björn Reuter.

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Reuter, B., Rodemer, C., Grudzenski, S. et al. Effect of Simvastatin on MMPs and TIMPs in Human Brain Endothelial Cells and Experimental Stroke. Transl. Stroke Res. 6, 156–159 (2015). https://doi.org/10.1007/s12975-014-0381-7

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  • DOI: https://doi.org/10.1007/s12975-014-0381-7

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