Dabravolski Siarhei A, Kashtalap Vasily V, Rozhkova Ulyana V, Maksaeva Anastasia O, Sukhorukov Vasily N, Orekhov Alexander N
Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel, 2161002, Israel.
Research Institute for Complex Issues of Cardiovascular Diseases, 6 Barbarash Boulevard, Kemerovo, 650002, Russia.
J Physiol Biochem. 2025 Jul 4. doi: 10.1007/s13105-025-01106-6.
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.
动脉粥样硬化是一种慢性炎症性疾病，涉及内皮细胞、平滑肌细胞和炎症介质之间的复杂相互作用。细胞间连接，包括黏附连接（AJs）、紧密连接（TJs）和缝隙连接（GJs），在维持血管完整性和调节血管壁细胞相互作用中起关键作用。本综述总结了这些连接对动脉粥样硬化产生影响的分子机制，重点关注关键蛋白，如血管内皮钙黏蛋白（VE-cadherin，AJs）、闭锁小带蛋白1（ZO-1）、闭合蛋白（occludin）、紧密连接蛋白（claudins，TJs）和连接蛋白（connexins，GJs）。由氧化应激、促炎细胞因子、易致动脉粥样硬化的剪切应力（aSS）和脂质介导的信号通路等因素驱动，这些连接的失调会导致内皮功能障碍、通透性增加、单核细胞浸润和斑块不稳定。此外，还探讨了包括核因子κB（NFκB）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）和Wnt/β-连环蛋白等信号通路在调节连接蛋白中的作用。包括氧化胆固醇、辐射和各种药物在内的新出现的因素为动脉粥样硬化中连接调节提供了新的见解。还讨论了靶向连接蛋白及其相关通路进行治疗干预的潜力。未来有必要开展聚焦于体内连接失调详细机制以及这些研究结果临床转化的研究，以开发针对动脉粥样硬化的新型治疗策略。临床试验编号：不适用。
