Chapter 4 - Endothelial Barrier: Factors That Regulate Its Permeability

Abstract

Endothelial barrier dysfunction leading to increased permeability and vascular leakage of plasma proteins is associated with several pathological conditions such as edema and sepsis. Several diseases and clinical conditions have been characterized as inflammatory due to new discoveries about disease-induced changes in endothelial cell function. Atherosclerosis, asthma, and diabetes are considered inflammatory diseases today. Even a clinical condition such as obesity may be classified as an inflammatory condition, with changes in endothelial function that may precede the appearance of more severe consequences of obesity such as diabetes or hypertension. Tropical parasite infection and angiogenesis are preceded by increased plasma leakage. It has become clear that inflammatory mediators induce interendothelial gaps as an essential mechanism for regulating paracellular permeability and transendothelial migration of leukocytes in many vascular beds of the systemic circulation. The endothelial cytoskeleton and VE-cadherin in the adherens junctions of postcapillary venules undergo dynamic and reversible reorganization to enable gap formation and closure. There are several physiological and pharmacological possibilities to stabilize the endothelial barrier through interference with the signaling mechanisms in postcapillary endothelial junctions and their VE-cadherin junction complexes eventually to counteract pathological plasma leakage.