{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T20:31:29Z","timestamp":1782160289047,"version":"3.54.5"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1057678"],"award-info":[{"award-number":["NRF-2019R1F1A1057678"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coxsackievirus and adenovirus receptor (CAR) is present in epithelial and vascular endothelial cell junctions. We have previously shown a hemorrhagic phenotype in germ-line CAR knock-out mouse embryos; we have also found that CAR interacts with ZO-1 and \u03b2-catenin. However, the role of CAR in vascular endothelial junction permeability has not been proven. To understand the roles of CAR in the vascular endothelial junctions, we generated endothelium-specific CAR knockout (CAR-eKO) mice. In the absence of CAR, the endothelial cell layer showed an increase in transmembrane electrical resistance (TER, \u2126) and coxsackievirus permeability. Evans blue dye and 70 kDa dextran-FITC were delivered by tail vein injection. We observed increased vascular permeability in the hearts of adult CAR-eKO mice compare with wild-type (WT) mice. There was a marked increase in monocyte and macrophage penetration into the peritoneal cavity caused by thioglycolate-induced peritonitis. We found that CAR ablation in endothelial cells was not significantly increased coxsackievirus B3 (CVB3) induced myocarditis in murine model. However, tissue virus titers were significantly higher in CAR-eKO mice compared with WT. Moreover, CVB3 was detected in the brain of CAR-eKO mice. Endothelial CAR deletion affects the expression of major endothelial junction proteins, such as cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1) in the cultured endothelial cells as well as liver vessel. We suggest that CAR expression is required for normal vascular permeability and endothelial tight junction homeostasis. Furthermore, CVB3 organ penetration and myocarditis severities were dependent on the endothelial CAR level.<\/jats:p>","DOI":"10.3390\/ijms22063053","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T05:43:26Z","timestamp":1615959806000},"page":"3053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Vascular Endothelial Integrity Affects the Severity of Enterovirus-Mediated Cardiomyopathy"],"prefix":"10.3390","volume":"22","author":[{"given":"Jin-Ho","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Hyeon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Seung","family":"Rhyu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Seok","family":"Jeon","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine 50 Irwon dong, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-1175","authenticated-orcid":false,"given":"Byung-Kwan","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1096\/fasebj.9.10.7615160","article-title":"Endothelial cell-to-cell junctions","volume":"9","author":"Dejana","year":"1995","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0092-8674(00)81279-9","article-title":"Cell adhesion: The molecular basis of tissue architecture and morphogenesis","volume":"84","author":"Gumbiner","year":"1996","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/(SICI)1097-4644(19960616)61:4<514::AID-JCB4>3.0.CO;2-R","article-title":"Cadherin-catenin complex: Protein interactions and their implications for cadherin function","volume":"61","author":"Aberle","year":"1996","journal-title":"J. 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