Endothelial junctional proteins (EJPs)

Endothelial junctional proteins are a diverse group of transmembrane and cytoplasmic proteins that form specialized structures between adjacent endothelial cells to regulate vascular integrity. These structures are primarily classified into adherens junctions, which provide mechanical strength through proteins like Vascular Endothelial (VE)-cadherin, and tight junctions, which control paracellular permeability via proteins such as Claudin-5 and Occludin (Dejana, 2004, Nat Rev Mol Cell Biol [1]). Gap junctions, composed of connexins, further facilitate direct metabolic and electrical communication between cells (Komarova et al., 2017, Front Physiol [2]). These proteins are essential for maintaining the blood-brain barrier and regulating the extravasation of fluids and leukocytes during the immune response. In pathological conditions like sepsis, chronic inflammation, and cancer, the disruption of these junctional complexes leads to excessive vascular leakage, tissue edema, and facilitated tumor cell intravasation (Giannotta et al., 2013, Adv Drug Deliv Rev [3]). Therapeutic strategies often focus on stabilizing these junctions to treat conditions like ARDS or diabetic macular edema, using agents that inhibit permeability factors like VEGF or activate stabilizing pathways like Tie2 (Greene et al., 2019, Arch Biochem Biophys [4]). Conversely, transiently opening these junctions is a major research focus for enhancing the delivery of neurotherapeutics across the blood-brain barrier. [1] https://pubmed.ncbi.nlm.nih.gov/14963368/ [2] https://pubmed.ncbi.nlm.nih.gov/28611671/ [3] https://pubmed.ncbi.nlm.nih.gov/23416303/ [4] https://pubmed.ncbi.nlm.nih.gov/30529351/

Other names

Endothelial cell-cell junctionsInterendothelial junctionsVascular junctional complexEndothelial barrier proteins

Stabilization of the endothelial barrier by preventing the disassembly, phosphorylation, or internalization of junctional complexes (e.g., VE-cadherin), often through the inhibition of VEGF signaling or activation of the Tie2/Angiopoietin-1 pathway.