Endothelial cell response to different mechanical forces

Endothelial cell response to different mechanical forces
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DOI:
10.1067/mva.2000.107989
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发表时间:
2000-10-01
影响因子:
4.3
通讯作者:
Sumpio, BE
Sumpio, BE
中科院分区:
医学2区
文献类型:
--
作者:
Azuma, N;Duzgun, A;Sumpio, BE

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目的:内皮细胞 (EC) 受到血流引起的物理力的影响。本研究的目的是直接比较培养的牛主动脉内皮细胞对循环应变和剪切应力的响应的内皮细胞信号通路。材料和方法将内皮细胞接种在柔性胶原蛋白I包被的硅胶膜上以检查循环应变的影响。使用 150 毫米汞柱真空以 60 循环/分钟的速率使膜变形长达 120 分钟。为了比较剪切应力的影响,将应变实验中使用的同一批次的 EC 接种在胶原蛋白 I 涂层的硅胶片上。然后使用平行室对 EC 进行 10 达因/厘米 (2) 剪切力长达 120 分钟。通过免疫印迹测定细胞外信号调节激酶 (ERK)、c-jun N 末端激酶 (JNK) 和 p38 的磷酸化来评估丝裂原激活蛋白激酶的激活。结果:ERR、JNK 和 p38 均被循环应变和剪切应力激活。循环应变和剪切应力都会激活 JNK。具有相似的时间模式和幅度,并在 30 分钟达到峰值。然而,与循环应变相比,剪切应力诱导 ERK 和 p38 更强烈、更快速的激活。结论:我们的结果表明,不同的机械力诱导丝裂原激活蛋白激酶的差异激活。这表明 EC 中可能存在不同的机械感受器来检测来自单个受体的不同力或替代耦合途径。
Purpose: Endothelial cells (ECs) are subjected to the physical forces induced by blood flow. The aim of this study was to directly compare the EC signaling pathway in response to cyclic strain and shear stress in cultured bovine aortic ECs.Materials and Methods The ECs were seeded on flexible collagen I-coated silicone membranes to examine the effect of cyclic strain. The membranes were deformed with a 150-mm Hg vacuum at a rate of 60 cycle/min for up to 120 minutes. For a comparison of the effect of shear stress, ECs from the same batch as used in the strain experiments were seeded on collagen I-coated silicone sheets. The ECs were then subjected to 10 dyne/cm(2) shear with the use of a parallel now chamber for up to 120 minutes. Activation of the mitogen-activated protein kinases was assessed by determining phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 with immunoblotting.Results: ERR, JNK and p38 were activated by both cyclic strain and shear stress. Both cyclic strain and shear stress activated JNK. with a similar temporal pattern and magnitude and a peak at 30 minutes. However, shear stress induced a more robust and rapid activation of ERK and p38, compared with cyclic strain.Conclusions: Our results indicate that different mechanical forces induced differential activation of mitogen-activated protein kinases. This suggests that there may be different mechanoreceptors in ECs to detect the different forces or alternative coupling pathways from a single receptor.