Effect of Fluid Shear Stress on Migration of Vascular Smooth Muscle Cells in Cocultured Model
Effect of Fluid Shear Stress on Migration of Vascular Smooth Muscle Cells in Cocultured Model
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DOI：
10.1007/s10439-005-9043-y
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发表时间：
2006-02
影响因子：
3.8
通讯作者：
N. Sakamoto;T. Ohashi;Masaaki Sato
中科院分区：
文献类型：
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作者：
N. Sakamoto;T. Ohashi;Masaaki Sato
增生中平滑肌细胞（SMC）的迁移被认为与血流状况相关。在本研究中，使用新设计的 EC-SMC 共培养模型 (CM) 研究了施加于内皮细胞 (EC) 的剪切应力对 SMC 迁移的影响，其中牛 SMC 和 EC 通过胶原层和滤膜分开。将 CM 暴露于 0.5、1.0 或 1.5 Pa 的剪切应力下 48 小时后，计算迁移到胶原层中的 SMC 数量。在静态条件下，与单独培养的 SMC 相比，CM 中 SMC 的迁移增加。与静态 CM 相比，1.5 Pa 的剪切应力显着抑制了 SMC 迁移 (p< 0.05)。通过酶谱分析，与静态 CM 相比，用暴露于 1.0 Pa (p< 0.05) 和 1.5 Pa (p< 0.005) 剪切应力的 CM 调节的培养基表现出活化基质金属蛋白酶-2 (MMP-2) 的减少。在培养基中添加一氧化氮 (NO) 合酶抑制剂 Nω-硝基-L-精氨酸甲酯可抑制 1.5 Pa 剪切应力对 SMC 迁移的影响，但 MMP-2 活性不受影响。这些结果表明生理剪切应力在动脉粥样硬化形成中具有保护作用。
Migration of smooth muscle cells (SMCs) in hyperplasia is thought to have a correlation with blood flow conditions. In this study, the effect of shear stress applied to endothelial cells (ECs) on SMC migration was examined using a newly designed EC–SMC coculture model (CM), in which bovine SMCs and ECs were separated by a collagen layer and a membrane filter. After exposing the CM to shear stresses of 0.5, 1.0, or 1.5 Pa for 48 h, the number of SMCs migrating into the collagen layer was counted. Under static conditions, the migration of SMCs in the CM increased compared with SMCs cultured alone. Shear stress of 1.5 Pa significantly suppressed the SMC migration (p< 0.05) compared with the static CM. Media conditioned with the CM exposed to shear stress of 1.0 Pa (p< 0.05) and 1.5 Pa (p< 0.005) exhibited reduction in activated matrix metalloproteinase-2 (MMP-2) compared with the static CM, as analyzed by zymography. Addition of an inhibitor of nitric oxide (NO) synthase,Nω-nitro-l-arginine methyle ester, to the media inhibited the effect of 1.5 Pa shear stress on SMC migration but MMP-2 activity was unaffected. These results suggest that physiological shear stress has protective roles in atherosclerogenesis.