Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress.
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-alpha 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 NFkappa 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 NFkappa 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 approximately 10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.
Tsou
Jean K
JK
Department of Biomedical Engineering, University of California, Davis, California, USA.
Gower
R Michael
RM
Ting
Harold J
HJ
Schaff
Ulrich Y
UY
Insana
Michael F
MF
Passerini
Anthony G
AG
Simon
Scott I
SI
D000293:Adolescent; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D033081:Shear Strength; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1