{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:21Z","timestamp":1760060601806,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial-to-mesenchymal transition (EndMT) is associated with various pathologies including cardiovascular, inflammatory, and fibrotic diseases or neoplasia. Concerning COVID-19, multiple organ dysfunctions and long COVID syndrome are mediated by microvascular damage and, recently, the role of SARS-CoV-2 peptide fragments in the induction of EndMT was demonstrated. Here, we investigated the immune-mediated effects of Spike S1 of SARS-CoV-2 on EndMT and demonstrated that cytokines secreted by S1-activated macrophages, mainly TNF\u03b1 + IFN\u03b3, also induce the phenotypical switch in HUVECs. In particular, a loss of the typical cobblestone morphology is observed, along with a huge reduction in endothelial adhesion molecules, such as vWF, CD31, and VE-cadherin, and a concomitant acquisition of mesenchymal markers, such as N-cadherin and FSP1 protein. In addition, the combined use of the drug infliximab, targeting TNF\u03b1, and baricitinib, an inhibitor of the JAK-STAT pathway, hinders the phenotypical changes by restoring the proper expression of endothelial markers. The protective effect of these drugs is evident not only when they are added to the culture medium together with the trigger, but also when added later, i.e., once EndMT has been started. These findings reinforce the role of COVID-19-associated cytokine storm in endothelial dysfunction and in the onset of the fibrotic process and sustain the clinical relevance of infliximab and baricitinib for the prevention of vascular damage.<\/jats:p>","DOI":"10.3390\/ijms26178672","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:53:01Z","timestamp":1757083981000},"page":"8672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baricitinib and Infliximab Mitigate the Endothelial-to-Mesenchymal Transition (EndMT) Induced by Cytokines in HUVECs"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2256-0530","authenticated-orcid":false,"given":"Amelia","family":"Barilli","sequence":"first","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Visigalli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-7783","authenticated-orcid":false,"given":"Giulia","family":"Recchia Luciani","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Crescini","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-0916","authenticated-orcid":false,"given":"Valeria","family":"Dall\u2019Asta","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Maria","family":"Rotoli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3390\/diagnostics14070711","article-title":"Long covid: Long-term impact of SARS-CoV-2","volume":"14","author":"Makhluf","year":"2024","journal-title":"Diagnostics"},{"key":"ref_2","first-page":"82","article-title":"Long COVID-19: A systematic review","volume":"71","author":"Karuturi","year":"2023","journal-title":"J. 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