Characterization of SMAD2 Activation in Human Thoracic Aortic Aneurysm

Abstract

Objective: Thoracic aortic aneurysm (TAA) reflects the local expansion of the thoracic aorta; the underlying causal molecular mechanism of TAA is not well understood. Recent studies have shown the importance of transforming growth factor beta (TGFbeta) signaling in Marfan and Loeys-Dietz syndromes; however, its role in non-familial, non-syndromic TAA remains unclear. Materials and Methods: We performed histochemical and immunohistochemical analyses for activated (phosphorylated) SMAD2 (P-SMAD2) as an indicator of TGFbeta signaling activities in the ascending TAA tissue as well as in the ascending aortic tissue with a normal diameter obtained from 7 patients without any clinical findings suggesting familial or syndromic TAA. Results: TAA samples showed a higher P-SMAD2-positive area than samples with a normal diameter. P-SMAD2 signal was higher in the outer zone of the aortic and TAA walls. Within the TAA tissue, P-SMAD2 staining showed the following two distinct patterns: layer-like staining at the border of the medial layer and the thickened intima and a spot-like staining within the medial layer surrounding the microvessels. Conclusion: These findings suggested that TGFbeta signaling is activated in several distinct histopathological contexts in TAA, suggesting a complex role of TGFbeta.