Aortic smooth muscle cells migration and the role of metalloproteinases and hyaluronan

Human aortic smooth muscle cells (AoSMCs) change their extracellular matrix composition during aging, with direct effects on cellular events and cell migration. For example, active matrix metalloproteinase-2 (MMP-2) is synthesized only by young AoSMCs, whereas aged cells produce only the inactive zymogen form. The pro-MMP-2 activation in young cells depends on an increase in membrane type 1 matrix metalloproteinase content. Furthermore, transcripts coding for tissue inhibitor of metalloproteinases (TIMPs) were upregulated in aged cells, and the increase of TIMPs also could prevent pro-MMP-2 activation. As consequence of these situations, young AoSMCs possess a higher migratory capability than aged cells on gelatin support. These data are confirmed by adding TIMP-1 and TIMP-2 to young cells which reproduces aged AoSMCs migratory behavior. The opposite effect was obtained in young cells silencing MMP-2 and TIMP-2.