© 1999 American Heart Association, Inc.
Cellular Biology |
Transient and Steady-State Effects of Shear Stress on Endothelial Cell Adherens Junctions
From the Vascular Research Laboratory, The Toronto Hospital Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. The current address for D.B.C. is Department of Anesthesia, Children's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Dr B.L. Langille, Vascular Research Laboratory, Toronto General Hospital, 200 Elizabeth St, CCRW 1-856, Toronto, Ontario, Canada M5G 2C4. E-mail lowell.langille{at}utoronto.ca
Abstract—Endothelial
cells exhibit profound changes in cell shape in response to altered
shear stress that may require disassembly/reassembly of adherens
junction protein complexes that mediate cell-cell adhesion. To test
this hypothesis, we exposed confluent porcine aortic
endothelial cells to 15 dyne/cm2 of shear
stress for 0, 8.5, 24, or 48 hours, using a parallel plate flow
chamber. Cells were fixed and stained with antibodies to vascular
endothelial (VE) cadherin, 
-catenin, ß-catenin, or
plakoglobin. Under static conditions, staining for all proteins was
intense and peripheral, forming a nearly continuous band
around the cells at cell-cell junctions. After 8.5 hours of shear
stress, staining was punctate and occurred only at sites of continuous
cell attachment. After 24 or 48 hours of shear, staining for
VE-cadherin, -catenin, and ß-catenin was intense and
peripheral, forming a band of "dashes" (adherens
plaques) that colocalized with the ends of stress fibers that inserted
along the lateral membranes of cells. Staining for plakoglobin was not
observed after 24 hours of shear stress, but returned after 48 hours.
Western blot analysis indicated that protein levels of
VE-cadherin, -catenin, and plakoglobin decreased, whereas
ß-catenin levels increased after 8.5 hours of shear stress. As cell
shape change reached completion (24 to 48 hours), all protein levels
were upregulated except for plakoglobin, which remained below control
levels. The partial disassembly of adherens junctions we have observed
during shear induced changes in endothelial cell shape
may have important implications for control of the
endothelial permeability barrier and other aspects of
endothelial cell function.
Key Words: shear stress • endothelium • vascular endothelial cadherin • -catenin • ß-catenin • plakoglobin
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