Ethanol inhibits pulse pressure-induced vascular smooth muscle cell migration by differentially modulating plasminogen activator inhibitor type 1, matrix metalloproteinase-2 and -9

John P. Cullen; Shariq Sayeed; Youngrin Kim; Nicholas G. Theodorakis; James V. Sitzmann; Paul A. Cahill; Eileen M. Redmond

doi:10.1160/TH05-03-0174

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(03): 639-645
DOI: 10.1160/TH05-03-0174

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Ethanol inhibits pulse pressure-induced vascular smooth muscle cell migration by differentially modulating plasminogen activator inhibitor type 1, matrix metalloproteinase-2 and -9

John P. Cullen

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

,

Shariq Sayeed

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

,

Youngrin Kim

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

,

Nicholas G. Theodorakis

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

,

James V. Sitzmann

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

,

Paul A. Cahill

¹Vascular Health Research Centre, Dublin City University, Dublin, Ireland

,

Eileen M. Redmond

²Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

› Author Affiliations

Abstract

Summary

We investigated the effect of ethanol on the pulse pressure-induced expression of PAI-1 and MMP-2/9 in human smooth muscle cells (SMC). Human SMC were exposed to static or pulse pressure (25 mL/min; pulse pressure 106/50 mm Hg) conditions for 24 h in the absence or presence of ethanol (0.1-100 mM). SMC migration was then measured byTranswell migration assay. SMC exposed to pulse pressure demonstrated a significant increase in PAI-1 mRNA and protein expression (∼4-fold and ∼3-fold) concomitant with a 3- and 8-fold increase in MMP-2 and MMP-9 protein, respectively. Ethanol dose-dependently inhibited the pulse pressure-induced SMC migration with complete inhibition observed at 20 mM. There was no effect of ethanol on basal PAI-1 or MMP-2/9 in SMC under static conditions. However, ethanol significantly enhanced the pulse pressure- induced PAI-1 mRNA and protein expression (2.2±0.52 fold and 2.5±0.27 fold, for 10 mM), respectively. In contrast, ethanol dose-dependently inhibited the pulse pressure-induced increases in MMP-9 protein and pro-MMP-9 activity and to a lesser extent MMP-2 mRNA and protein and pro-MMP-2 activity, with significant inhibition observed at 1 mM. These data provide a molecular mechanism mediating the inhibitory effect of ethanol on pulse-pressure-induced SMC migration and may be relevant to the cardioprotective effects of ethanol in vivo.

Keywords

Cell migration - smooth muscle cells - proteases/inhibitors - alcohol - hemodynamic forces

Full Text

References

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