Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress

Jean K. Tsou, R. Michael Gower, Harold J. Ting, Ulrich Y. Schaff, Michael F. Insana, Anthony G. Passerini, Scott I. Simon

Research output: Contribution to journalArticle

Abstract

Objective: Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense a gradient of fluid shear stress and transduce signals that regulate membrane expression of cell adhesion molecules and monocyte recruitment. Methods: Human aortic endothelial cells were stimulated with TNF-α and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm2. Cell adhesion molecule expression and activation of NFκ B were quantified by immunofluorescence microscopy with resolution at the level of a single endothelial cell. Monocyte recruitment was imaged using custom microfluidic flow chambers. Results: VCAM-1 and E-selectin upregulation was greatest between 2-4 dyne/cm2 (6 and 4-fold, respectively) and above 8 dyne/cm2 expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NFκ B nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm2. Monocyte recruitment was most efficient in regions where E-selectin and VCAM-1 expression was greatest. Conclusions: We found that the endothelium can sense a change in shear stress on the order of 0.25 dyne/cm2 over a length of ∼10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.

Original languageEnglish (US)
Pages (from-to)311-323
Number of pages13
JournalMicrocirculation
Volume15
Issue number3
StatePublished - Apr 2008

Keywords

  • Atherosclerosis
  • Endothelium
  • Inflammation
  • Monocyte
  • Shear stress gradient

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Cardiology and Cardiovascular Medicine

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    Tsou, J. K., Gower, R. M., Ting, H. J., Schaff, U. Y., Insana, M. F., Passerini, A. G., & Simon, S. I. (2008). Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. Microcirculation, 15(3), 311-323.