title: Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB.
abstract: 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.
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK. r.pedrigi@imperial.ac.uk.
authors: Ryan M
authors: RM
authors: Pedrigi
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Konstantinos I
authors: KI
authors: Papadimitriou
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Avinash
authors: A
authors: Kondiboyina
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Sukhjinder
authors: S
authors: Sidhu
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: James
authors: J
authors: Chau
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Miten B
authors: MB
authors: Patel
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Daniel C
authors: DC
authors: Baeriswyl
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Emmanuel M
authors: EM
authors: Drakakis
authors: Department of Bioengineering, Imperial College London, Prince Consort Rd., London, SW7 2AZ, UK.
authors: Rob
authors: R
authors: Krams
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D013314:Stress, Mechanical
chemical_list: D016328:NF-kappa B
keywords: Advanced plaques; Atherosclerosis; Biomechanics; Fluid–structure interaction; Mechanobiology; Nuclear factor kappa b; Shear stress; Strain; Thin cap fibroatheroma