Study of the Effect of Hemodynamic Forces on Mechanism of Atherogenesis using Cocultured Blood Vessel Model

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This project investigated the mechanism of development of atherosclerosis using endothelial-smooth muscle cell (EC-SMC) cocultured blood vessel model and obtained the following results.1.Migration of SMCs in the cocultured blood vessel models increased about 1.8 times higher than that in the model constructed with SMCs only. Exposure the cocultured model to fluid shear stress resulted in suppression of SMC migration. The migration of SMCs was not decreased by exposure to shear stress with medium containing an inhibitor of nitric oxide (NO) synthase. Theses results indicate that EC derived NO suppresses the migration of SMC under shear condition.2.There was no significant difference in permeability of EC monolayer between cocultured model and EC monocultured model under static culture condition. Shear stress deceased significantly EC permeability in the cocultured model. EC permeability in the monocultured model did not significantly change by exposure to shear stress. This result suggests that SMCs may have an important role in EC permeability.3.Under the static condition, the number of leukocytes adhered to ECs in the cocultured model was about 1.8 time higher than that in the EC monocultured model. After exposure to shear stress, there were not difference in the number of adhered leukocytes between cocultured and EC monocultured models. Shear stress did not influence on leukocyte adhesion in the EC monocultured model. These results indicate that shear stress suppressed leukocyte-EC adhesion increased by SMC derived physiological active substances in the cocultured model.These results lead to the conclusion that the cellular interaction between ECs and SMCs is modulated by shear condition and have critical roles in the development of atherosclerosis.