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Am J Physiol Heart Circ Physiol 273: H2396-H2405, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2396-H2405, November 1997

Role of cadherins and plakoglobin in interendothelial adhesion under resting conditions and shear stress

Hans-Joachim Schnittler, Bernd Püschel, and Detlev Drenckhahn

Institute of Anatomy, University of Würzburg, D-97070 Würzburg, Germany

The role of cadherins and the cadherin-binding cytosolic protein plakoglobin in intercellular adhesion was studied in cultured human umbilical venous endothelial cells exposed to fluid shear stress. Extracellular Ca2+ depletion (<10-7 M) caused the disappearance of both cadherins and plakoglobin from junctions, whereas the distribution of platelet endothelial cell adhesion molecule 1 (PECAM-1) remained unchanged. Cells stayed fully attached to each other for several hours in low Ca2+ but began to dissociate under flow conditions. At the time of recalcification, vascular endothelial (VE) cadherin and beta -catenin became first visible at junctions, followed by plakoglobin with a delay of ~20 min. Full fluid shear stress stability of the junctions correlated with the time course of the reappearance of plakoglobin. Inhibition of plakoglobin expression by microinjection of antisense oligonucleotides did not interfere with the junctional association of VE-cadherin, PECAM-1, and beta -catenin. The plakoglobin-deficient cells remained fully attached to each other under resting conditions but began to dissociate in response to flow. Shear stress-induced junctional dissociation was also observed in cultures of plakoglobin-depleted arterial endothelial cells of the porcine pulmonary trunk. These observations show that interendothelial adhesion under hydrodynamic but not resting conditions requires the junctional location of cadherins associated with plakoglobin. beta -Catenin cannot functionally compensate for the junctional loss of plakoglobin, and PECAM-1-mediated adhesion is not sufficient for monolayer integrity under flow.

adhesion molecules; vascular endothelial cadherin; catenins; platelet endothelial cell adhesion molecule 1; antisense oligonucleotides


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