Details

Autor(en) / Beteiligte

• Claesson-Welsh, Lena
• Dejana, Elisabetta
• McDonald, Donald M.

Titel

Permeability of the Endothelial Barrier: Identifying and Reconciling Controversies

Ist Teil von

• Trends in molecular medicine, 2021-04, Vol.27 (4), p.314-331

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Leakage from blood vessels into tissues is governed by mechanisms that control endothelial barrier function to maintain homeostasis. Dysregulated endothelial permeability contributes to many conditions and can influence disease morbidity and treatment. Diverse approaches used to study endothelial permeability have yielded a wealth of valuable insights. Yet, ongoing questions, technical challenges, and unresolved controversies relating to the mechanisms and relative contributions of barrier regulation, transendothelial sieving, and transport of fluid, solutes, and particulates complicate interpretations in the context of vascular physiology and pathophysiology. Here, we describe recent in vivo findings and other advances in understanding endothelial barrier function with the goal of identifying and reconciling controversies over cellular and molecular processes that regulate the vascular barrier in health and disease. In the microcirculation, endothelial permeability varies from least in arterioles to greatest in venules and is regulated in an organ-specific manner to control the extravasation of fluid, solutes, and large molecules.Inflammatory factors increase vascular permeability by inducing the formation of focal endothelial gaps that can be transient in acute inflammation or sustained in chronic conditions.Gap formation requires changes in the organization of tight junctions and adherens junctions that join endothelial cells and create a barrier.Adherens junction opening requires phosphorylation, loss of homophilic interactions, and internalization of VE-cadherin accompanied by changes in the cortical cytoskeleton.Sustained hyperpermeability in pathologic conditions can lead to edema, reduced vascular perfusion, impaired drug delivery, and exaggerated disease severity.