{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:52:45Z","timestamp":1791665565331,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007496","name":"CARIGE","doi-asserted-by":"publisher","award":["D.R. 3707"],"award-info":[{"award-number":["D.R. 3707"]}],"id":[{"id":"10.13039\/501100007496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The mechanisms by which hyperuricemia induces vascular dysfunction and contributes to cardiovascular disease are still debated. Phenotypic transition is a property of vascular smooth muscle cells (VSMCs) involved in organ damage. The aim of this study was to investigate the effects of uric acid (UA) on changes in the VSMC cytoskeleton, cell migration and the signals involved in these processes. MOVAS, a mouse VSMC line, was incubated with 6, 9 and 12 mg\/dL of UA, angiotensin receptor blockers (ARBs), proteasome and MEK-inhibitors. Migration property was assessed in a micro-chemotaxis chamber and by phalloidin staining. Changes in cytoskeleton proteins (Smoothelin B (SMTB), alpha-Smooth Muscle Actin (\u03b1SMA), Smooth Muscle 22 Alpha (SM22\u03b1)), Atrogin-1 and MAPK activation were determined by Western blot, immunostaining and quantitative reverse transcription PCR. UA exposition modified SMT, \u03b1SMA and SM22\u03b1 levels (p &lt; 0.05) and significantly upregulated Atrogin-1 and MAPK activation. UA-treated VSMCs showed an increased migratory rate as compared to control cells (p &lt; 0.001) and a re-arrangement of F-actin. Probenecid, proteasome inhibition and ARBs prevented the development of dysfunctional VSMC. This study shows, for the first time, that UA-induced cytoskeleton changes determine an increase in VSMC migratory rate, suggesting UA as a key player in vascular remodeling.<\/jats:p>","DOI":"10.3390\/ijms24032960","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"2960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Role of Uric Acid in Vascular Remodeling: Cytoskeleton Changes and Migration in VSMCs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1279-3178","authenticated-orcid":false,"given":"Elisa","family":"Russo","sequence":"first","affiliation":[{"name":"Nephrology and Dialysis Unit, San Luca Hospital, 55100 Lucca, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bertolotto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Zanetti","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Picciotto","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-5586","authenticated-orcid":false,"given":"Pasquale","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-4078","authenticated-orcid":false,"given":"Federico","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-8729","authenticated-orcid":false,"given":"Fabrizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-872X","authenticated-orcid":false,"given":"Roberto","family":"Pontremoli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6432-2429","authenticated-orcid":false,"given":"Giacomo","family":"Garibotto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-7043","authenticated-orcid":false,"given":"Francesca","family":"Viazzi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verzola","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40885-022-00206-5","article-title":"Validation of age- and sex-dependent association of uric acid and incident hypertension in rural areas","volume":"28","author":"Kim","year":"2022","journal-title":"Clin. 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