Department of Biomedical Engineering, University of Virginia, Box 800759, Health System, Charlottesville, Virginia 22908, USA.
Nat Commun. 2013;4:1525. doi: 10.1038/ncomms2530.
Haemodynamic variations are inherent to blood vessel geometries (such as bifurcations) and correlate with regional development of inflammation and atherosclerosis. However, the complex frequency spectrum characteristics from these haemodynamics have never been exploited to test whether frequency variations are critical determinants of endothelial inflammatory phenotype. Here we utilize an experimental Fourier transform analysis to systematically manipulate individual frequency harmonics from human carotid shear stress waveforms applied in vitro to human endothelial cells. The frequency spectrum, specifically the 0 th and 1st harmonics, is a significant regulator of inflammation, including NF-κB activity and downstream inflammatory phenotype. Further, a harmonic-based regression-model predicts eccentric NF-κB activity observed in the human internal carotid artery. Finally, short interfering RNA-knockdown of the mechanosensor PECAM-1 reverses frequency-dependent regulation of NF-κB activity. Thus, PECAM-1 may have a critical role in the endothelium's exquisite sensitivity to complex shear stress frequency harmonics and provide a mechanism for the focal development of vascular inflammation.
血流动力学变化是血管几何形状（如分叉）所固有的，并与炎症和动脉粥样硬化的区域性发展相关。然而，这些血流动力学的复杂频谱特征从未被开发利用，以测试频率变化是否是内皮炎症表型的关键决定因素。在这里，我们利用实验傅里叶变换分析，系统地从体外施加于人内皮细胞的人颈动脉壁切应力波中操纵单个频率谐波。频谱，特别是 0 次和 1 次谐波，是炎症的重要调节因子，包括 NF-κB 活性和下游炎症表型。此外，基于谐波的回归模型预测了在人颈内动脉中观察到的偏心 NF-κB 活性。最后，机械传感器PECAM-1 的短干扰 RNA 敲低逆转了 NF-κB 活性的频率依赖性调节。因此，PECAM-1 在血管内皮细胞对复杂壁切应力频率谐波的敏感性中可能具有关键作用，并为血管炎症的局灶性发展提供了一种机制。
