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

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)898-909
Number of pages12
JournalAnnals of biomedical engineering
Volume45
Issue number4
DOIs
StatePublished - Apr 1 2017

Keywords

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

ASJC Scopus subject areas

  • Biomedical Engineering

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    Pedrigi, R. M., Papadimitriou, K. I., Kondiboyina, A., Sidhu, S., Chau, J., Patel, M. B., Baeriswyl, D. C., Drakakis, E. M., & Krams, R. (2017). Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB. Annals of biomedical engineering, 45(4), 898-909. https://doi.org/10.1007/s10439-016-1750-z