The elastin-laminin receptor functions as a mechanotransducer in vascular smooth muscle

Laminin and elastin, two major constituents of the extracellular matrix, bi nd to cells via the elastin-laminin receptor (ELR), a receptor distinct fro m integrins. Despite the ubiquitous nature of elastin and laminin in the ma trix, the consequences of activation of the ELR are unknown. Because integr ins are capable of mechanosensitive transduction, we hypothesized that the ELR would exert a similar function. Accordingly, we examined the effects of cyclical stretch on canine coronary smooth muscle gene expression and prol iferation that are mediated by the ELR. Northern blot analyses showed a 31% decrease in serum-induced expression of c-fos when cells were stretched fo r 30 min on elastin, but no change in expression was observed on collagen. Serum-induced proliferation of stretched cells was markedly attenuated on e lastin when compared with collagen. Both the molecular (decreased c-fos exp ression) and biological (decreased proliferation) responses on elastin were restored after blockade of the ELR with the elastin fragment hexapeptide ( valine-glycine-valine-alanine-proline-glycine, VGVAPG). The inhibition was specific for this peptide, as another hydrophobic hexapeptide (valine-serin e-leucine-serine-proline- glycine, VSLSPG) did not inhibit the responses. T hese results demonstrate that cyclic stretch inhibits c-fos expression and proliferation of coronary vascular smooth muscle cells grown on elastin mat rixes, a mechanosensitive response that is transduced by the ELR.