Abstract 294: Differential Expression of Hedgehog/Notch and Transforming Growth Factor-ß in Human Abdominal Aortic Aneurysms
Objective: The molecular mechanisms leading to the development of Adnominal Aortic Aneurysms (AAA) remain poorly understood. The aim of this study was to determine the expression of Sonic Hedgehog (SHh), Transforming Growth Factor Beta (TGF-β) and Notch signaling components in aneurysmal and non-aneurysmal aorta in vivo and demonstrate SHh control of Notch, TGF- β1 and SMC differentiation in vitro.
Methods: Paired tissue samples were obtained from aneurysmal and non-aneurysmal (control) segments of the aortic wall of at least 8 patients with suitable anatomy undergoing open repair of infrarenal AAA. Protein and mRNA expression levels were determined by western blot analysis and quantitative Real-time PCR.
Results: Aneurysm development resulted in a significant reduction in vascular smooth muscle (vSMC) differentiation gene protein and mRNA levels for α-actin and SMC22α, respectively. In parallel, significant reductions in Hh and Notch signaling component expression was observed in aneurysmal tissue when compared to control, concurrent with increased TGF-β1 expression. In vitro, Hh signaling inhibition with cyclopamine (40μmol/L) treatment for 24 h in human aortic smooth muscle cells (HASMC), resulted in decreased Hh/Notch signaling component and vSMC differentiation gene expression. Moreover, cyclopamine significantly increased TGF-β1 mRNA expression.
Conclusion: These results suggest that SHh/Notch and TGFβ signaling are differentially regulated in aneurysmal tissue, compared with non-aneurysmal tissue. Changes in these signaling pathways and the resulting changes in vSMC content may play a causative role in the development of AAA.
Author Disclosures: A. Doyle: None. E.M. Redmond: None. J.P. Cullen: None. P.A. Cahill: None. D. Morrow: None.
- © 2014 by American Heart Association, Inc.