{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:55:14Z","timestamp":1787507714434,"version":"build-2736575974"},"reference-count":246,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Occludin (OCLN), a core transmembrane protein found in tight junctions, plays a key role in cardiovascular homeostasis by maintaining vascular endothelial barrier integrity and regulating intercellular signaling and metabolic activities. Recent evidence indicates that OCLN dysfunction is closely related to the pathological processes of various cardiovascular and cerebrovascular diseases such as ischemic stroke, atherosclerosis, and hypertensive encephalopathy. Its downregulation of expression or structural damage can directly destroy the blood\u2013brain barrier and peripheral vascular barrier and aggravate vascular leakage, inflammatory cell infiltration, and neuronal damage; OCLN regulates the activity of signaling pathways, such as NF-\u03baB and MAPK, through interaction with proteins such as ZO-1 and claudins, affecting inflammatory response, oxidative stress, and cell apoptosis. New evidence further reveals the non-classical function of OCLN in mediating endothelial autophagy, mitochondrial function, and metabolic reprogramming, suggesting the multidimensionality of its mechanism of action. However, the upstream and downstream regulatory networks of OCLN, tissue-specific expression differences, and their feasibility as therapeutic targets remain controversial. This systematic review examines the progress of research on the molecular mechanisms of OCLN in cardiovascular and cerebrovascular diseases, integrating its dual role in barrier damage, inflammatory cascades, and cell death, and explores potential therapeutic strategies targeting OCLN to repair barriers or regulate related signaling pathways to provide new ideas for precise intervention in cardiovascular and cerebrovascular diseases.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1701272","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:32:37Z","timestamp":1778214757000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Occludin-mediated barrier dysfunction and its role in cardiovascular and cerebrovascular pathogenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei","family":"Xu","sequence":"first","affiliation":[{"name":"Clinical Medical College\/Affiliated Hospital of Jiujiang University","place":["Jiujiang, Jiangxi, China"]},{"name":"Jiujiang Clinical Precision Medicine Research Center","place":["Jiujiang, Jiangxi, China"]},{"name":"Jiangxi Provincial Clinical Research Center for Laboratory Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongzhang","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangxi Polytechnic University","place":["Jiujiang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Long","sequence":"additional","affiliation":[{"name":"Clinical Medical College\/Affiliated Hospital of Jiujiang University","place":["Jiujiang, Jiangxi, China"]},{"name":"Jiujiang Clinical Precision Medicine Research Center","place":["Jiujiang, Jiangxi, China"]},{"name":"Jiangxi Provincial Clinical Research Center for Laboratory Medicine","place":["Nanchang, Jiangxi, 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