{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:33:35Z","timestamp":1772804015182,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil effective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA\/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients\u2019 aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF-\u03b21 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA\/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients\u2019 TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA\/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.<\/jats:p>","DOI":"10.3390\/cells9010154","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T03:07:11Z","timestamp":1578539231000},"page":"154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cyclophilin A\/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-6040","authenticated-orcid":false,"given":"Gianluca L.","family":"Perrucci","sequence":"first","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7291-5811","authenticated-orcid":false,"given":"Erica","family":"Rurali","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Corlian\u00f2","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Balzo","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-4863","authenticated-orcid":false,"given":"Michela","family":"Piccoli","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-8539","authenticated-orcid":false,"given":"Donato","family":"Moschetta","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Pini","sequence":"additional","affiliation":[{"name":"Centro Malattie Rare, Marfan Clinic, U.O. Cardiologia, ASST FBF-Sacco, 20157 Milan, Italy"},{"name":"Centro di Cardiogenetica Vascolare, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Gaetano","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche (CNR), Istituto di Ricerca e di Innovazione Biomedica (IRIB), 90146 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Antona","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche e Cliniche \u201cL. Sacco\u201d, Universit\u00e0 degli Studi, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5242-150X","authenticated-orcid":false,"given":"Gustavo","family":"Egea","sequence":"additional","affiliation":[{"name":"Departament Biomedicina, Universitat de Barcelona and Institut d\u2019Investigacions M\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter","family":"Fischer","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Male\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Enzymology department, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Alamanni","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Chirurgia Cardiaca, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"},{"name":"Dipartimento di Scienze Cliniche e di Comunit\u00e0, Universit\u00e0 degli Studi, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Cogliati","sequence":"additional","affiliation":[{"name":"Treviso Tissue Bank Foundation, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Paolin","sequence":"additional","affiliation":[{"name":"Treviso Tissue Bank Foundation, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Pompilio","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"},{"name":"Dipartimento di Scienze Cliniche e di Comunit\u00e0, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Dipartimento di Chirurgia Cardiovascolare, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Nigro","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(05)67789-6","article-title":"Marfan\u2019s syndrome","volume":"366","author":"Judge","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/352337a0","article-title":"Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ymgme.2012.07.023","article-title":"Structure and function of the mammalian fibrillin gene family: Implications for human connective tissue diseases","volume":"107","author":"Davis","year":"2012","journal-title":"Mol. 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