{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:37:06Z","timestamp":1789425426535,"version":"build-2803163510"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:p>Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose aetiology is still debated, have focused mainly on severe dilatations. In the present study, we aimed to detect earlier signs of aortopathy. Specimens were collected from the \u2018concavity\u2019 (lesser curvature) and the \u2018convexity\u2019 (greater curvature) of mildly dilated AAs (ascending aortas; diameter \u22644\u00a0cm) with stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas. Specimens were submitted to morphometry, immunohistochemistry and differential gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype, remodelling, MF (myofibroblast) differentiation and TGF\u03b2 (transforming growth factor \u03b2) pathway. Smoothelin and myocardin mRNAs decreased in all the samples from patients, with the exception of those from BAV convexity, where a change in orientation of smoothelin-positive SMCs and an increase of \u03b1-SMA (\u03b1-smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients showed both shared and distinct alterations concerning the TGF\u03b2 pathway, including an increased TGF\u03b2 and TGF\u03b2R2 (TGF\u03b2 receptor 2) expression in both groups and a decreased TGF\u03b2R1 expression in BAV samples only. Despite a decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN (fibronectin) in the BAV convexity, the onset of the expression of the corresponding protein in the media was observed in dilated aortas, whereas the normal media from donors was negative for this isoform. This discrepancy could be related to modifications in the intima, normally expressing ED-A FN and showing an altered structure in mild aortic dilatations in comparison with donor aorta. Our results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis. The defective expression of TGF\u03b2R1\u00a0in BAV might be a constitutive feature, while other changes we reported could be influenced by haemodynamics.<\/jats:p>","DOI":"10.1042\/cs20120324","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T08:22:43Z","timestamp":1343982163000},"page":"97-108","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Early cell changes and TGF\u03b2 pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis"],"prefix":"10.1042","volume":"124","author":[{"given":"Amalia","family":"Forte","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Della Corte","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Grossi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Bancone","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaela","family":"Provenzano","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Finicelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"De Feo","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca\u00a0S.","family":"De Santo","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianantonio","family":"Nappi","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Cotrufo","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Cipollaro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,9,26]]},"reference":[{"key":"2021113010250361100_B1","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1001\/jama.2011.1286","article-title":"Incidence of aortic complications in patients with bicuspid aortic valves","volume":"306","author":"Michelena","year":"2011","journal-title":"JAMA, J. 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