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-beta in
aneurysms related to Marfan (and
Loeys-Dietz) syndrome. Here we investigate
TGF-beta 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-beta1 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged
TGF-beta1 mRNA level. The increase in stored
TGF-beta1 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-beta1 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-beta retention and Smad2 signalling in syndromic and non-syndromic
aneurysms of the ascending aorta.