THE MOLECULAR ORGANIZATION OF ENDOTHELIAL JUNCTIONS IN VASCULAR PERMEABILITY

Vascular permeability is an innate function of the circulatory system that regulates the flux of fluid,

proteins, and immune cells from blood to tissue. Vascular permeability is regulated by a molecular

mechanism that involves the endothelial barrier. Endothelial barrier function and vascular

permeability are regulated by intercellular junctions that control the extravasation of plasma and its

macromolecular constituents. The number and arrangement of these junctions determine

permeability differences in the vasculature in an organ- and tissue-specific manner. The barrier is

mediated by endothelial cell-cell adhesions. Adjacent endothelial cells are connected by protein

complexes that are part of the Gap junctions (GJs), adherens junctions (AJs), Tight junctions (TJs),

and additional other adhesion receptors such as CD31/Platelet Endothelial Cell Adhesion Molecule-

1 (PECAM-1) and nectins, which are connected to the actin cytoskeleton via different adaptor

molecules. This review focuses on the molecular organization and regulation of endothelial

junctions in vascular permeability in health and disease. Additional work should also be directed to

the understanding of mechanisms that influence altered vascular permeability in specific diseases

and to strategies for preventing or reversing vascular leakage, which can result in harmful

consequences