Cyclic strain-induced endothelial MMP-2: role in vascular smooth muscle cell migration

Biochemical and Biophysical Research Communications
Nicholas von Offenberg SweeneyP A Cahill

Abstract

Matrix metalloproteinases (MMPs) play a vital role in vasculature response to hemodynamic stimuli via the degradation of extracellular matrix substrates. In this study, we investigated the putative role of cyclic strain-induced endothelial MMP-2 (and MMP-9) expression and release in modulating bovine aortic smooth muscle cell (BASMC) migration in vitro. Equibiaxial cyclic strain of bovine aortic endothelial cells (BAECs) leads to elevation in cellular MMP-2 (and MMP-9) expression, activity, and secretion into conditioned media, events which were time- and force-dependent. Subsequent incubation of BASMCs with conditioned media from chronically strained BAECs (5%, 24 h) significantly reduces BASMC migration (38+/-6%), an inhibitory effect which could be completely reversed by targeted siRNA 'knock-down' of MMP-2 (but not MMP-9) expression and activity in BAECs. Moreover, inhibition of strain-mediated MMP-2 expression in BAECs by protein tyrosine kinase (PTK) blockade with genistein (50 microM) was also found to completely reverse this inhibitory effect on BASMC migration. Finally, direct supplementation of recombinant MMP-2 into the BASMC migration assay was found to have no significant effect on migration. However, the effect on...Continue Reading

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Citations

Jul 10, 2007·Biomechanics and Modeling in Mechanobiology·G P RaeberJ A Hubbell
Apr 23, 2010·Biological & Pharmaceutical Bulletin·Ming-Kun LuPin-Shern Chen
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Sep 5, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Philip M CumminsPaul A Cahill

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