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Recent experimental studies reported an activation of TGF\u2010\u03b2 in aneurysms related to Marfan (and Loeys\u2010Dietz) syndrome. Here we investigate TGF\u2010\u03b2 signalling in normal and pathological human ascending aortic wall in syndromic and non\u2010syndromic aneurysmal disease. Aneurysmal ascending aortic specimens, classified according to aetiology: syndromic MFS (<jats:italic>n<\/jats:italic> = 15, including two mutations in <jats:italic>TGFBR2<\/jats:italic>), associated with BAV (<jats:italic>n<\/jats:italic> = 15) or degenerative forms (<jats:italic>n<\/jats:italic> = 19), were examined. We show that the amounts of TGF\u2010\u03b21 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged <jats:italic>TGF\u2010<\/jats:italic>\u03b2<jats:italic>1<\/jats:italic> mRNA level. The increase in stored TGF\u2010\u03b21 was associated with enhanced LTBP\u20101 protein and mRNA levels. These dysregulations of the extracellular ligand are associated with higher phosphorylated Smad2 and <jats:italic>Smad2<\/jats:italic> mRNA levels in the ascending aortic wall from all types of aneurysm. This activation correlated with the degree of elastic fibre fragmentation. Surprisingly, there was no consistent association between the nuclear location of pSmad2 and extracellular TGF\u2010\u03b21 and LTBP\u20101 staining and between their respective mRNA expressions. In parallel, decorin was focally increased in aneurysmal media, whereas biglycan was globally decreased in aneurysmal aortas. In conclusion, this study highlights independent dysregulations of TGF\u2010\u03b2 retention and Smad2 signalling in syndromic and non\u2010syndromic aneurysms of the ascending aorta. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2516","type":"journal-article","created":{"date-parts":[[2009,1,6]],"date-time":"2009-01-06T08:35:21Z","timestamp":1231230921000},"page":"131-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["Syndromic and non\u2010syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway"],"prefix":"10.1002","volume":"218","author":[{"given":"Delphine","family":"Gomez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Al Haj Zen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano 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