A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms
A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms
复制标题
DOI：
10.1115/1.1486468
复制
发表时间：
2002-08-01
影响因子：
1.7
通讯作者：
Gimbrone, MA
中科院分区：
文献类型：
--
作者：
Blackman, BR;García-Cardeña, G;Gimbrone, MA
在循环中，排列在血管腔中的流动响应性内皮细胞（EC）持续暴露于复杂的血液动力学力。为了增加我们对EC对这些动态剪切力的反应的理解，开发了一种新的体外流动模型来模拟动脉循环中内皮细胞所遇到的脉动剪切应力波形。一个修改后的波形在人体腹主动脉的流动模式建模，用于评估人脐静脉内皮细胞对这种新型的刺激的生物反应性。使用无流动（静态）培养条件作为基线，将24小时的动脉脉动流与等效时间平均稳定层流剪切应力进行比较。虽然这两种流动刺激诱导细胞形状和排列的变化相当，不同的反应模式中观察到的分布肌动蛋白应力纤维和长春纽蛋白相关的粘附复合物，内在的迁移特性，和eNOS mRNA和蛋白质的表达。因此，这些结果揭示了EC对动脉波形的独特响应性，并开始阐明内皮对整个人类血管树的流动的动态特性的复杂传感能力。
In the circulation, flow-responsive endothelial cells (ECs) lining the lumen of blood vessels are continuously exposed to complex hemodynamic forces. To increase our understanding of EC response to these dynamic shearing forces, a novel in vitro flow model was developed to simulate pulsatile shear stress waveforms encountered by the endothelium in the arterial circulation. A modified waveform modeled after flow patterns in the human abdominal aorta was used to evaluate the biological responsiveness of human umbilical vein ECs to this new type of stimulus. Arterial pulsatile flow for 24 hours was compared to an equivalent time-average steady laminar shear stress, using no flow (static) culture conditions as a baseline. While both flow stimuli induced comparable changes in cell shape and alignment, distinct patterns of responses were observed in the distribution of actin stress fibers and vinculin-associated adhesion complexes, intrinsic migratory characteristics, and the expression of eNOS mRNA and protein. These results thus reveal a unique responsiveness of ECs to an arterial waveform and begin to elucidate the complex sensing capabilities of the endothelium to the dynamic characteristics of flows throughout the human vascular tree.