{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:06Z","timestamp":1787028666152,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570507"],"award-info":[{"award-number":["82570507"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400498"],"award-info":[{"award-number":["82400498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0526400"],"award-info":[{"award-number":["2024ZD0526400"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["GZB20230045"],"award-info":[{"award-number":["GZB20230045"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Objectives: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease with limited effective diagnostic and therapeutic strategies. Although endothelial barrier dysfunction represents an early event in TAAD pathogenesis, the role of endothelial tight junction proteins remains largely undefined. In this study, we systematically explored the function of claudin-5 (CLDN5), an endothelial-specific tight junction sealing protein, in TAAD through integrated bioinformatic, clinical, and experimental approaches. Materials and Methods: In the study, we combined bioinformatic analysis of the CLDN5 gene with clinical and cellular investigations. The clinical cohort included 44 patients with thoracic aortic dissection (TAAD) and 41 healthy controls. Plasma CLDN5 levels were measured by ELISA. Cellular studies involved treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-\u03b1 (TNF-\u03b1) and performing CLDN5 knockdown, with barrier function assessed using transendothelial electrical resistance and permeability assays. Results: Plasma CLDN5 was significantly elevated in TAAD patients (14.20 \u00b1 1.394 ng\/mL) compared to controls (6.061 \u00b1 0.8208 ng\/mL, p &lt; 0.05) and showed strong diagnostic potential with an area under the receiver operating characteristic curve (AUC) of 0.7877 (95% CI: 0.6897\u20130.8857). In cellular experiments, TNF-\u03b1 treatment induced the release of CLDN5 fragments into the supernatant and reduced membrane CLDN5. Furthermore, CLDN5 knockdown directly impaired endothelial barrier function. Conclusions: Our findings identify CLDN5 as a promising circulating biomarker for TAAD diagnosis and provide new insights into TAAD pathogenesis, offering potential diagnostic strategies.<\/jats:p>","DOI":"10.3390\/jcm15031219","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"1219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Endothelial Barrier Dysfunction to Circulating Biomarker: Clinical Potential of Claudin-5 in Thoracic Aortic Aneurysm and Dissection"],"prefix":"10.3390","volume":"15","author":[{"given":"Qianhui","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitian","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzheng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University School of Basic Medical Sciences, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109485","DOI":"10.1016\/j.cellsig.2019.109485","article-title":"Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease","volume":"66","author":"Cong","year":"2020","journal-title":"Cell Signal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/ijnp\/pyac079","article-title":"Inflammation and Blood-Brain Barrier in Depression: Interaction of CLDN5 and IL6 Gene Variants in Stress-Induced Depression","volume":"26","author":"Gal","year":"2023","journal-title":"Int. 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