Premium
Syndromic and non‐syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway
Author(s) -
Gomez Delphine,
Al Haj Zen Ayman,
Borges Luciano F,
Philippe Monique,
Gutierrez Paulo Sampaio,
Jondeau Guillaume,
Michel JeanBaptiste,
Vranckx Roger
Publication year - 2009
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2516
Subject(s) - ascending aorta , biglycan , aneurysm , aortic aneurysm , medicine , marfan syndrome , extracellular matrix , aorta , decorin , pathological , pathology , biology , microbiology and biotechnology , surgery , proteoglycan
Common features such as elastic fibre destruction, mucoid accumulation, and smooth muscle cell apoptosis are co‐localized in aneurysms of the ascending aorta of various aetiologies. Recent experimental studies reported an activation of TGF‐β in aneurysms related to Marfan (and Loeys‐Dietz) syndrome. Here we investigate TGF‐β signalling in normal and pathological human ascending aortic wall in syndromic and non‐syndromic aneurysmal disease. Aneurysmal ascending aortic specimens, classified according to aetiology: syndromic MFS ( n = 15, including two mutations in TGFBR2 ), associated with BAV ( n = 15) or degenerative forms ( n = 19), were examined. We show that the amounts of TGF‐β1 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged TGF‐ β 1 mRNA level. The increase in stored TGF‐β1 was associated with enhanced LTBP‐1 protein and mRNA levels. These dysregulations of the extracellular ligand are associated with higher phosphorylated Smad2 and Smad2 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‐β1 and LTBP‐1 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‐β retention and Smad2 signalling in syndromic and non‐syndromic aneurysms of the ascending aorta. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.