Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells
Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells
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DOI：
10.1007/s10439-016-1626-2
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发表时间：
2016-10-01
影响因子：
3.8
通讯作者：
Haribabu, Bodduluri
中科院分区：
文献类型：
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作者：
Chakraborty, Amlan;Chakraborty, Sutirtha;Haribabu, Bodduluri
本研究证明了振荡壁切应力（WSS）的方向性对增殖和促动脉粥样硬化基因表达（I-CAM，E-选择素，和IL-6）的存在下，炎症介质白三烯B-4（LTB 4）和细菌脂多糖（LPS）从内皮细胞生长在轨道培养皿的影响。计算流体动力学（CFD）被应用到量化的流动在菜，而一个分析解决方案，代表了斯托克斯第二问题的扩展被用于验证。结果表明，WSS的大小是相对恒定的中心附近的盘和侧壁附近的振荡显着（0-0.9帕）。实验表明，LTB 4主导了细胞增殖和面积的剪切效应。加入LPS对细胞增殖无明显影响，但对细胞面积有明显影响。I-CAM 1，E-选择素和IL-6的表达被改变的方向振荡剪切指数（DOSI，测量的双轴振荡剪切），但不剪切幅度。DOSI与其他致动脉粥样硬化因子相互作用的强度进一步加强了其重要性。因此，剪切的方向性似乎是调节基因表达的一个重要因素，并提供了一个潜在的解释的倾向增加血管病变的区域中的动脉与振荡双轴流。
This study demonstrated the effects of the directionality of oscillatory wall shear stress (WSS) on proliferation and proatherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of inflammatory mediators leukotriene B-4 (LTB4) and bacterial lipopolysaccharide (LPS) from endothelial cells grown in an orbiting culture dish. Computational fluid dynamics (CFD) was applied to quantify the flow in the dish, while an analytical solution representing an extension of Stokes second problem was used for validation. Results indicated that WSS magnitude was relatively constant near the center of the dish and oscillated significantly (0-0.9 Pa) near the side walls. Experiments showed that LTB4 dominated the shear effects on cell proliferation and area. Addition of LPS didn't change proliferation, but significantly affected cell area. The expression of I-CAM1, E-Selectin and IL-6 were altered by directional oscillatory shear index (DOSI, a measure of the biaxiality of oscillatory shear), but not shear magnitude. The significance of DOSI was further reinforced by the strength of its interactions with other atherogenic factors. Hence, directionality of shear appears to be an important factor in regulating gene expression and provides a potential explanation of the propensity for increased vascular lesions in regions in the arteries with oscillating biaxial flow.