Wall Shear Stress Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells Depending on a TGF-β1 Manner

Background: Venous intimal hyperplasia (VIH) is the main cause of arteriovenous fistula (AVF) dysfunction. Hemodynamic forces have an important role in VIH. The proliferation and migration of vascular smooth muscle cells (VSMCs) play a crucial role in the development of VIH and TGF-β1 just has the biological function of inducing proliferation and migration of VSMCs. We use parallel plate flow chamber system to simulate different shear stress and investigate whether shear stress regulate VSMCs proliferation and migration through TGF-β1 Methods: Shear stress (SS) was simulated with an ECs/VSMCs cocultured parallel plate flow chamber system. The coculture system was established by plating cells on the two sides of polyethylene terephthalate membrane. The EC side was subjected to different shear stress (Low-SS, Normal-SS and Oscillating-SS), whereas the opposite VSMCs side was maintained under static conditions. Computational fluid dynamics were applied to three-dimensional models of ECs/VSMCs cocultured flow chamber system to estimate the velocity and WSS. The expression of TGF-β1 were analyzed by immunofluorescence assay. VSMCs proliferation and migration assay was performed with the BrdU kit and Transwell system. Results: The expression of TGF-β1 was significantly up-regulated following application of Low-SS and Oscillating-SS, and the distribution of TGF-β1 was transferred to the cell membrane, compared with the static group. The migration and proliferation of cocultured VSMCs were significantly up-regulated after Low-SS and Oscillating-SS. Conclusion: Our results suggest that Low-SS and Oscillating-SS exerts atherosclerotic influences on the ECs and VSMCs in a TGF-β1-dependent process. TGF-β1 increases the proliferation and migration of VSMC and is thought to be a pro-atherogenic effect, which can be used as a new therapeutic target for the treatment of AVF dysfunction. The formation and development of VIH in AVF may be a local hyperplasia process by shear stress-TGF-β1 regulation, which provides new insights into the mechanisms of neointimal hyperplasia.