| Autor: |
Pedrigi RM; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK. r.pedrigi@imperial.ac.uk., Papadimitriou KI; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Kondiboyina A; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Sidhu S; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Chau J; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Patel MB; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Baeriswyl DC; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Drakakis EM; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK., Krams R; Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK. |
| Abstrakt: |
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-κB. 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-κB (p = 0.09 and p < 0.001, respectively). Multidirectional stretch also promoted significant nuclear NF-κB 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. |
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