SHEAR-STRESS INDUCES TRANSFORMING GROWTH FACTOR-BETA(1) RELEASE BY ARTERIAL ENDOTHELIAL-CELLS

Background. Myointimal hyperplasia is a common complication after vasc ular reconstruction. Increasing shear stress has been shown to reduce formation of myointimal hyperplasia. The aims of our study were (1) to analyze the correlation between shear stress and release of transform ing growth factor (TGF)-beta(1) by endothelial cells and (2) to determ ine the effect of TGF-beta(1) on smooth muscle cell proliferation. Met hods. Bovine arterial endothelial cells were subjected to increasing s hear stress in an in vitro serum-free system. The release of TGF-beta( 1) by endothelial cells was assessed by enzyme-linked immunosorbent as say and Western blot analysis. The effect of TGF-beta(1) on the prolif eration of the subconfluent monolayer of bovine smooth muscle cells wa s determined by tritiated thymidine uptake. Results. Shear stress indu ced a significant increase of the release of TGF-beta(1) by endothelia l cells (p < 0.001). This phenomenon was proportional to the level of shear stress. The amount of TGF-beta(1) released by endothelial cells subjected to shear stress had a significant inhibitory effect on growt h rate and tritiated thymidine uptake of smooth muscle cells. Conclusi ons. On the basis of the results of our study, we conclude that increa sing shear stress induces release of TGF-beta(1) by arterial endotheli al cells in a concentration that has a clear inhibitory effect on smoo th muscle cell proliferation. This phenomenon could explain the inhibi tory effect of increasing shear stress on the formation of myointimal hyperplasia.