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

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 upregulationwas 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 number4
DOIs
StatePublished - May 2008

Fingerprint

Cell Adhesion Molecules
Endothelial Cells
Inflammation
Monocytes
E-Selectin
Vascular Cell Adhesion Molecule-1
Microfluidics
Intercellular Adhesion Molecule-1
Fluorescence Microscopy
Endothelium
Atherosclerosis
Arteries
Membranes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Cardiology and Cardiovascular Medicine

Cite this

Tsou, J., Gower, R. M., Ting, H. J., Schaff, U., 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(4), 311-323. https://doi.org/10.1080/10739680701724359

Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. / Tsou, Jean; Gower, R. Michael; Ting, Harold J.; Schaff, Ulrich; Insana, Michael F.; Passerini, Anthony G.; Simon, Scott I.

In: Microcirculation, Vol. 15, No. 4, 05.2008, p. 311-323.

Research output: Contribution to journalArticle

Tsou, J, Gower, RM, Ting, HJ, Schaff, U, Insana, MF, Passerini, AG & Simon, SI 2008, 'Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress', Microcirculation, vol. 15, no. 4, pp. 311-323. https://doi.org/10.1080/10739680701724359
Tsou, Jean ; Gower, R. Michael ; Ting, Harold J. ; Schaff, Ulrich ; Insana, Michael F. ; Passerini, Anthony G. ; Simon, Scott I. / Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. In: Microcirculation. 2008 ; Vol. 15, No. 4. pp. 311-323.
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