Endothelial Barrier Function under Laminar Fluid Shear Stress

Abstract

SUMMARY:It has been suggested that increasing levels of shear stress could modify endothelial permeability. This might be critical in venous grafting and in the pathogenesis of certain vascular diseases. We present a novel setup based on impedance spectroscopy that allows online investigation of the transendothelial electrical resistance (TER) under pure laminar shear stress. Shear 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. Confluent cultures of porcine pulmonary trunk endothelial cells typically displayed a TER between 6 and 15 ⍀cm 2 under both resting conditions and low shear stress levels (0.5 dyn/cm 2 ). Raising shear stress to the range 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. Subsequently, TER slowly decreased to a minimum of 20% below the starting value. During this period, acceleration of shape change occurred. In the ensuing period, TER values recovered, reaching control levels within hours and associated with an entire deceleration of shape change. A heterogeneous distribution of ␣-, ␤-, and ␥-catenin, main components of the endothelial adherens type junctions, was also observed, indicating a differentiated regulation of shear stress-induced junction rearrangement. Additionally, catenins were partly colocalized with ␤-actin at the plasma membrane, indicating migration activity of these subcellular parts. Shear stress, even at peak levels of 50 dyn/cm 2 , did not cause intercellular gap formation. These data show that endothelial monolayers exposed to increased levels of laminar shear stress respond with a shear stress-dependent regulation of permeability and a reorganization of junction-associated proteins, whereas monolayer integrity remains unaffected. (Lab Invest 2000, 80:1819 -1831.

Lymphatic Endothelial Cells Adapt Their Barrier Function in Response to Changes in Shear Stress

“…11 In cultured vascular endothelial cell models, increasing t causes an initial rapid increase in barrier function, followed by decrease in barrier function over longer periods of time. [8][9][10] In both of the isolated venule and cultured endothelial cell models, the effects of increased t were reversed upon returning to the baseline t. [8][9][10][11] These studies demonstrate that shear stress sensing is an important property of vascular endothelium for regulating barrier function.…”

“…7 In blood vessels and in cultured vascular endothelial cell models, changes in the laminar fluid flow rate can influence barrier function. [8][9][10][11] For example, increasing the fluid flow through isolated, perfused coronary venules not only increases filtration of solutes, but also increases their diffusive permeability coefficient to albumin through a NO-related mechanism. 11 In cultured vascular endothelial cell models, increasing t causes an initial rapid increase in barrier function, followed by decrease in barrier function over longer periods of time.…”

“…Using cultured lymphatic endothelial cells, and based on evidence that step increases in t transiently increase barrier function of vascular endothelial cells. 8,9 we tested the hypothesis that a step elevation of t rapidly enhances barrier function. In addition, we evaluated whether protein kinase A (PKA) or the small GTPase Rac1, both of which have been implicated as promoters of enhanced endothelial barrier function, 12 may be involved in shear stress-induced changes in lymphatic endothelial barrier function.…”

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

“…Similar permeability characteristics have been reported previously for endothelial cells when they are exposed to FSS, where the permeability increases immediately at the onset of flow and slowly plateaus to a baseline value. 42,43 The introduction of flow does bring about a transient increase in permeability for the BAOEC layer that stabilizes after about 2.5 h of flow. Thus, it is safe to assume that this study is performed on a BAOEC layer that has been primed to flow, and the study performed after 6 h of exposure to FSS will not be affected by any initial flow related changes in permeability.…”

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

“…However, in vivo HBMEC are shown to interact with astrocytes and also exposed to shear stress through blood flow. Several lines of evidence suggest that non-human brain and non-brain endothelial tight junctions are enhanced when co-cultured with astrocytes or in the presence of ACM [1,5,56,61,62,69,81], and blood flow associated shear stress have been shown to modify the endothelial barrier [67,70,74].…”