{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:18:09Z","timestamp":1790680689506,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K24AR063120"],"award-info":[{"award-number":["K24AR063120"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Intravenous iloprost improves Raynaud\u2019s phenomenon (RP) and promotes healing of digital ulcers in systemic sclerosis (SSc; scleroderma). Despite a short half\u2010life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE\u2010cadherin clustering between endothelial cells (ECs), regulate endothelial properties including barrier function, endothelial\u2010to\u2010mesenchymal transition (EndoMT), and angiogenesis. We undertook this study to investigate the hypothesis that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE\u2010cadherin and increased permeability in SSc ECs (<jats:italic>P<\/jats:italic> &lt; 0.05). Iloprost increased VE\u2010cadherin clustering at junctions and restored junctional levels of VE\u2010cadherin in SSc ECs (mean \u00b1 SD 37.3 \u00b1 4.3 fluorescence units) compared to normal ECs (mean \u00b1 SD 29.7 \u00b1 3.4 fluorescence units; <jats:italic>P<\/jats:italic> &lt; 0.05), after 2 hours of iloprost incubation. In addition, iloprost reduced permeability of monolayers, increased tubulogenesis, and blocked EndoMT in both normal and SSc ECs (n \u2265 3; <jats:italic>P<\/jats:italic> &lt; 0.05). The effects in normal ECs were inhibited by a function\u2010blocking antibody that prevents junctional clustering of VE\u2010cadherin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that the long\u2010lasting effects of iloprost reflect its ability to stabilize adherens junctions, resulting in increased tubulogenesis and barrier function and reduced EndoMT. These findings provide a mechanistic basis for the use of iloprost in treating SSc patients with RP and digital ulcers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41536","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T04:22:50Z","timestamp":1601526170000},"page":"520-529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-9115","authenticated-orcid":false,"given":"Pei\u2010Suen","family":"Tsou","sequence":"first","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"Palisoc","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann 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