Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-kappa B

作者：Pedrigi Ryan M; Papadimitriou Konstantinos I; Kondiboyina Avinash; Sidhu Sukhjinder; Chau James; Patel Miten B; Baeriswyl Daniel C; Drakakis Emmanuel M; Krams Rob

来源：Annals of Biomedical Engineering, 2017, 45(4): 898-909.

DOI：10.1007/s10439-016-1750-z

• Atherosclerosis
• Mechanobiology
• Biomechanics
• Strain
• Shear stress
• Fluid-structure interaction
• Advanced plaques
• Thin cap fibroatheroma
• Nuclear factor kappa b

Exposure of endothelial cells to low and multidirectional blood flow is known to promote a pro-atherogenic phenotype. The mechanics of the vessel wall is another important mechano-stimulus within the endothelial cell environment, but no study has examined whether changes in the magnitude and direction of cell stretch can be pro-atherogenic. Herein, we developed a custom cell stretching device to replicate the in vivo stretch environment of the endothelial cell and examined whether low and multidirectional stretch promote nuclear translocation of NF-kappa B. A fluid-structure interaction model of the device demonstrated a nearly uniform strain within the region of cell attachment and a negligible magnitude of shear stress due to cyclical stretching of the cells in media. Compared to normal cyclical stretch, a low magnitude of cyclical stretch or no stretch caused increased expression of nuclear NF-kappa B (p = 0.09 and p < 0.001, respectively). Multidirectional stretch also promoted significant nuclear NF-kappa B expression, comparable to the no stretch condition, which was statistically higher than the low (p < 0.001) and normal (p < 0.001) stretch conditions. This is the first study to show that stretch conditions analogous to atherogenic blood flow profiles can similarly promote a pro-atherogenic endothelial cell phenotype, which supports a role for disturbed vessel wall mechanics as a pathological cell stimulus in the development of advanced atherosclerotic plaques.

• 出版日期2017-4