The role of cell junctions in atherosclerosis: implications for inflammation, endothelial dysfunction, and plaque stability.

Abstract

Atherosclerosis, a chronic inflammatory disease, involves a complex interplay between endothelial cells, smooth muscle cells, and inflammatory mediators. Cell-to-cell junctions, including adherens junctions (AJs), tight junctions (TJs), and gap junctions (GJs), play a critical role in maintaining vascular integrity and regulating cellular interactions in the vascular wall. This review summarises the molecular mechanisms by which these junctions contribute to atherosclerosis, focusing on key proteins like VE-cadherin (AJs), ZO-1, occludin, and claudins (TJs), and connexins (GJs). Dysregulation of these junctions, driven by factors such as oxidative stress, pro-inflammatory cytokines, atheroprone shear stress (aSS), and lipid-mediated signalling pathways, leads to endothelial dysfunction, increased permeability, monocyte infiltration, and plaque instability. Furthermore, the role of signalling pathways, including NFκB, PI3K/AKT, and Wnt/β-catenin, in the regulation of junctional proteins is explored. Emerging factors, including oxygenated cholesterol, radiation, and various drugs, provide new insights into junctional modulation in atherosclerosis. The potential of targeting junctional proteins and their associated pathways for therapeutic interventions is also discussed. Future studies focusing on the detailed mechanisms of junctional dysregulation in vivo and the clinical translation of these findings are necessary to develop novel therapeutic strategies for atherosclerosis. Clinical trial number Not applicable.