Positive Correlation Between the Dysregulation of Transforming Growth Factor-β₁ and Aneurysmal Pathological Changes in Patients With Marfan Syndrome

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Background: Our goal was to investigate the correlation between the dysregulation of transforming growth factor-β₁ (TGF-β₁) and cystic medial degeneration in the aortic aneurysmal tissues of in Marfan syndrome (MFS) patients. Although aortic aneurysm in animal models of MFS is related to the dysregulation of TGF-β, it has yet to be determined whether TGF-β dysregulation correlates with pathogenic aneurysmal characteristics in MFS patients. Methods and Results: Compared with aortic tissue from normal individuals, the medial layers of aortic tissue from MFS patients exhibited profound cystic medial degeneration and cellular apoptosis. These histopathologic changes positively correlated with the extent of TGF-β₁ signaling activation (Smad2 phosphorylation) in aneurysmal aortic tissue. In addition, the level of TGF-β₁ expression in peripheral blood and aneurysmal aortic tissues was significantly elevated in MFS patients. A significant positive correlation was observed between the plasma level of active TGF-β₁ in MFS patients and the severity of cystic medial degeneration and Smad2 phosphorylation in aneurysmal aortic medial layers. Conclusions: We found a strong association between the dysregulation of TGF-β₁ and aortic pathogenesis in human MFS patients. This suggests that the plasma concentration of TGF-β₁ in MFS patients might be a useful biomarker of the progression of aortic aneurysms.  (Circ J 2013; 77: 952–958)