Fluid shear stress inhibits vascular smooth muscle cell migration in vitro

Vascular smooth muscle cells (SMCs) are exposed directly to blood flow and fluid-induced shear stress (SS) in injured blood vessels and are also exposed to SS in intact vessels via interstitial flow driven by the transmural pressure gradient, It has been shown that abnormally high SMC migration from the vessel's media to its intima is one of the contributing factors to intimal hyperplasia development. These observations considered in concert provide the basis for our study of the effects of SS on SNIC migration. We have previously shown (BMES 2000, 2001) that SS applied to rat aortic SMCs in vitro acts to suppress SMC migration through Matrigel-coated filters. This inhibition is at least partly due to the reduction in activation of matrix metalloproteinase-2, which is involved in SMC extracellular matrix degradation, a fundamental process in SMC migration. Platelet-derived growth factor (PDGF)-AA has also been shown to be much less chemoattractive to SMCs than PDGF-BB, Studies are currently underway to determine the role of SS in the production of PDGF-AA by SMCs, another potential contributor to the SS-induced inhibition of SMC migration.