Maria D’Apolito, Giovanna D’Andrea, Anna Laura Colia, Rosa Santacroce, Maurizio Margaglione, Angela Bruna Maffione
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.