Endothelial barrier function under laminar fluid shear stress

It has been suggested that increasing levels of shear stress could modify e ndothelial permeability. This might be critical in venous grafting and in t he pathogenesis of certain vascular diseases. We present a novel setup base d on impedance spectroscopy that allows online investigation of the transen dothelial electrical resistance (TER) under pure laminar shear stress. Shea r stress-induced change in TER was associated with changes in cell motility and cell shape as a function of time (morphodynamics) and accompanied by a reorganization of catenins that regulate endothelial adherens junctions. C onfluent cultures of porcine pulmonary trunk endothelial cells typically di splayed a TER between 6 and 15 Omega cm(2) under both resting conditions an d low shear stress levels (0.5 dyn/cm(2)). Raising shear stress to the rang e of 2 to 50 dyn/cm(2) caused a transient 2% to 15% increase in TER within 15 minutes that was accompanied by a reduction in cell motility. Subsequent ly, TER slowly decreased to a minimum of 20% below the starting value. Duri ng this period, acceleration of shape change occurred. In the ensuing perio d, TER values recovered, reaching control levels within hours and associate d with an entire deceleration of shape change. A heterogeneous distribution of alpha-, beta-, and gamma -catenin, main components of the endothelial a dherens type junctions, was also observed, indicating a differentiated regu lation of shear stress-induced junction rearrangement. Additionally, cateni ns were partly colocalized with beta -actin at the plasma membrane, indicat ing migration activity of these subcellular parts. Shear stress, even at pe ak levels of 50 dyn/cm2, did not cause intercellular gap formation. These d ata show that endothelial monolayers exposed to increased levels of laminar shear stress respond with a shear stress- dependent regulation of permeabi lity and a reorganization of junction-associated proteins, whereas monolaye r integrity remains unaffected.