Mechanics of Endothelial Cell Architecture and Vascular Permeability

Abstract

Blood vessel walls form a selective barrier to the transport of materials between blood and tissue, and the endothelium contributes significantly to this barrier function. The role of the endothelium is particularly important in thin-walled vessels, such as venules, because during tissue inflammation the endothelial junctions widen in localized areas and gaps form, thus compromising the barrier function. The mechanisms of endothelial gap formation are still under question. In this review we describe what is known about the structure of endothelial cell-cell junctions and how this structure can change during inflammation. We then consider two possible mechanisms by which endothelial gaps are formed: active endothelial cell contraction or breakdown of the junctional complex, followed by passive recoil. Using measured values of the mechanical properties of endothelial cells, and the forces to which they are subjected, we calculate that gap formation by breakdown of cellular adhesion, followed by passive recoil, is a feasible mechanism. Finally, since endothelial cell surfaces, including junctions, are coated with a glycocalyx, we consider the question of whether changes in the glycocalyx can markedly increase endothelial permeability. We conclude that gap formation can occur by active contraction or by breakdown of adhesion, depending on the inflammatory mediator, and that the responses of the glycocalyx may also play an important role in the regulation of microvascular permeability.

Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases

“…These results suggest that the inhibition of transendothelial permeability and migration derives from the inhibition of p38-mediated formation of stress fibres. Interestingly, formation of stress fibres also requires phosphorylation of myosin light chain (MLC) to trigger the association of F-actin with myosin (Schnittler et al, 1990;Garcia et al, 1995;Baldwin and Thurston, 2001). In this context, we found that the activation of E-selectin Figure 3 Activation of E-selectin increases transendothelial permeability -HUVEC were cultivated at confluence on a 0.4 mm pore size gelatinized polycarbonate membranes that separate the upper and bottom part of a 6.5 mm modified Boyden chamber.…”

“…E-selectin-mediated activation of ERK regulates transendothelial permeability and migration of cancer cells by regulating the Src-dependent dissociation of the VE-cadherin/b-catenin complex Adherens junctions are major structures involved in the regulation of transendothelial permeability and migration of cancer cells and leucocytes across a monolayer of endothelial cells including HUVEC (Baldwin and Thurston, 2001;Yuan, 2002;Ionescu et al, 2003;Peng et al, 2005). As a major component of adherens junctions, VE-cadherin connects adjacent endothelial cells through its extracellular domain, whereas its intracellular domain interacts with actin cytoskeleton via a family of catenins namely b-catenin (Dejana et al, 1999).…”

“…This requires an increase in transendothelial permeability, a highly regulated process that involves weakening of cell adhesion to extracellularmatrix, loss of cellular junctions and the active or passive retraction of the endothelial cells (Baldwin and Thurston, 2001). The process is reversible, which indicates that endothelial cells can restore tight and adherens junctions following their dissolution.…”

Endothelial cell functions

“…The endothelial lining presents a large surface area for this exchange of materials between blood and tissues (Baldwin and Thurston, 2001). The total area of this interface in human has been estimated to be about 350 m 2 (Pries et al, 2000).…”

Change in shear stress (Δτ)/hydraulic conductivity (Lp) relationship after pronase treatment of individual capillaries in situ

“…Microvessel permeability also has been associated with the luminal glycocalyx (Baldwin and Thurston, 2001;Curry and Michel, 1980;Michel and Curry, 1999). van den Berg et al (2003) used hyaluronidase to target hyaluronan, a component of the glycocalyx, and demonstrated that enzyme digestion not only decreased thickness of the glycocalyx, but also increased the pericapillary space, indicative of myocardial tissue edema.…”