Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes.

Abstract:

BACKGROUND AND PURPOSE:Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation. METHODS:Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure. RESULTS:Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L). CONCLUSIONS:Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke.

journal_name

Stroke

journal_title

Stroke

authors

Wang S,Lee SR,Guo SZ,Kim WJ,Montaner J,Wang X,Lo EH

doi

10.1161/01.STR.0000226923.48905.39

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

1910-2

issue

7

eissn

0039-2499

issn

1524-4628

pii

01.STR.0000226923.48905.39

journal_volume

37

pub_type

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