Interstitial flow induces MMP-1 expression and SMC migration in 3-D collagen I gels via an ERK1/2-c-Jun pathway and mechanosenation by heparan sulfate proteoglycans and focal adhesions

The migration of vascular smooth muscle cells (SMCs) and fibroblasts into the intima after vascular injury is a central process in vascular lesion formation. The elevation of transmural interstitial flow is also observed after damage to the vascular endothelium. We have previously shown that interstitial flow promotes vascular cell motility in 3-D collagen I gels via upregulation of MMP-1. In this work, we further reveal that interstitial flow-induced MMP-1 expression and cell migration proceeds through the ERK1/2-c-Jun pathway. We also show that heparin sulfate proteoglycans (HSPGs) and focal adhesion kinase (FAK) are sensors and transmitters which convert the interstitial flow stimulus to biomolecular responses and altered cell function (migration). Our findings suggest that interstitial flow shear stress may play an important role in migration of SMCs and fibroblasts during neointima formation and vascular remodeling.