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01-04-2015 | Brief Communications

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

Authors: Björn Reuter, Claus Rodemer, Saskia Grudzenski, Stephen Meairs, Peter Bugert, Michael G. Hennerici, Marc Fatar

Published in: Translational Stroke Research | Issue 2/2015

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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Title: Effect of Simvastatin on MMPs and TIMPs in Human Brain Endothelial Cells and Experimental Stroke
Authors: Björn Reuter
Claus Rodemer
Saskia Grudzenski
Stephen Meairs
Peter Bugert
Michael G. Hennerici
Marc Fatar
Publication date: 01-04-2015
Publisher: Springer US
Published in: Translational Stroke Research / Issue 2/2015
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-014-0381-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

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Springer Medicine

Abstract

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