Fluid shear stress-induced reorganization of adherens junctions in human endothelial cells

1999 1999

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Abstract (summary)

Flow-induced changes in confluent human umbilical vein endothelial cell (HUVEC) monolayers were studied using a parallel-plate flow system. Static-cultured endothelial cells, in monolayers, are polygonal in shape. When exposed to shear stress, HUVEC aligned and elongated parallel to the direction of flow. We postulated that the interendothelial cell junctions would remodel in response to continuous fluid shear stress. Shear stress-induced morphological reorganization of the F-actin cytoskeleton is synchronized with the remodeling of the adherens junctions. These junctions are comprised of VE-cadherin and associated [special characters omitted]-catenin, [special characters omitted]-catenin, [special characters omitted]-catenin and p120-catenin. Under static conditions, the junctional VE-cadherin complexes in HUVEC form intricate, three-dimensional lattice-like structures. Over a time course of exposure to shear stress these intricate structures are remodeled into compact, uniform cell-cell junctions that outline cell contours. Immunoblot analyses of differential detergent extracts prepared from HUVEC monolayers were used to determine whether the expression and cytoskeletal association of the VE-cadherin complex proteins changed in response to shear stress. The quantities of VE-cadherin and [special characters omitted]-catenin increased in the cytoskeletal fractions from sheared HUVEC, suggesting that there was increased cell-cell junctional stability in endothelial cells exposed to continuous fluid shear stress. Shear stress stimulated increased tyrosine phosphorylation of VE-cadherin-associated [special characters omitted]-catenin, [special characters omitted]-catenin and p120-catenin, possibly dynamically modulating the disassembly and re-assembly of cadherin complexes during junctional remodeling. Such changes in tyrosine phosphorylation are regulated by the integrated actions of protein tyrosine kinases and phosphatases. In static-cultured HUVEC, SHP2, an intracellular protein tyrosine phosphatase, co-precipitated with VE-cadherin-associated [special characters omitted]-catenin. The association between SHP2 and VE-cadherin complexes was greatly diminished in extracts from cells exposed to fluid shear stress. Shear-induced increases of tyrosine phosphorylation in the VE-cadherin complex correlated with the loss of SHP2 from the adherens junctions. This implicates SHP2 as part of the kinase/phosphatase mechanism that regulates the remodeling of the adherens junctions during endothelial cell adaptation to fluid shear stress. The shear-mediated dissociation of SHP2 from VE-cadherin complexes also correlated with an increased association of SHP2 with PECAM-1. Thus, in endothelial cells fluid shear stress appears to regulate SHP2 association with its junctional protein partners as HUVEC dramatically remodeled their cell-cell junctions.

Indexing (details)

Cellular biology;
0379: Cellular biology
0786: Biophysics
Identifier / keyword
Biological sciences; Adherens junctions; Endothelial cells; Fluid shear stress-induced; Shear stress
Fluid shear stress-induced reorganization of adherens junctions in human endothelial cells
Ukropec, Jon Alec
Number of pages
Publication year
Degree date
School code
DAI-B 60/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
9780599227446, 0599227443
Woolkalis, Marilyn J.
Thomas Jefferson University
University location
United States -- Pennsylvania
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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