Abstract 2675: Up-Regulated Transforming Growth Factor-β1 Co-Localized with Elastin Lamella in Aortic Wall Contributes to Thoracic Aortic Dissection
Background- As an important multifunctional regulator of extracellular matrix (ECM), Transforming Growth Factor(TGF)- β1 has been documented to be involving in abdominal aortic aneurysm, however the mechanism by which TGF-β1 remodels the extracellular matrix (ECM) within aortic wall of thoracic aortic dissection (TAD) remained undetermined.
Methods and Results- To analyze the alteration of TGF-β1 and its relationship with ECM in dissecting aortic wall, aortic specimens taken from TAD operative patients (n=20) at UCLA medical center and organ donor (n=20) as control were prepared with paraffin embedded tissue slide, activated TGF-β1 and α-smooth muscle actin were examined with double immunofluorescent stain and semiquantified by fluorescent intensity analysis. Simultaneously, histopathological investigation of ECM was accomplished by Verhoeff van-Gieson (EVG) and Masson’s trichrome (MT) stain. Immunofluorescence analysis demonstrated activated TGF-β1 expression was highest in media, followed by intima and lowest in adventitia of aortic wall for both TAD patients and control. Morphologically, TGF-β1 was characterized with disarrayed fragments or continuous lamella in media and exactly overlapped with elastin lamellae in media. TAD patients exhibited higher TGF-β1 expression of 109.56% to control by entire aortic wall (P<0.05) , 116.09% (P<0.05) in media and 116.75% (P<0.05) in adventitia by corresponding layers, but no difference detected for intima between two groups. TGF-β1 distribution histogram analysis disclosed activated TGF-β1 condensed at the elastin lamellae of media and was higher by 34.83% in TAD patients compared to control (p<0.01). A strengthened actin expression in media of TAD was determined as well. Histopathologically, TAD exhibited attenuated and interrupted elastin lamellae in media and reinforced collagen in media and adventitia.
Conclusions- TGF-β1 expression is upregulated and unevenly distributed in dissecting aortic wall of TAD patients. Significant up-regulation of activated TGF-β1 condensed at the elastin lamella of media, this implicates a crucial role of TGF-β1 modulation on elastin in evolution of aortic dissection.