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Updated: Jul 5, 2026
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
Published on: March 8, 2019
Altered transforming growth factor-beta signaling in a murine model of thoracic aortic aneurysm
Jeffrey A Jones1, John R Barbour, Robert E Stroud
1Department of Surgery, Division of Cardiothoracic Surgery Research, Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29425, USA. jonesja@musc.edu
Objective:
Thoracic aortic aneurysms (TAAs) develop by a multifactorial process involving maladaptive signaling pathways that alter the aortic vascular environment. Transforming growth factor-beta (TGF-beta) has been implicated in regulating the structure and composition of the extracellular matrix by differential activation of various intracellular signaling pathways. However, whether and to what degree TGF-beta signaling contributes to TAA development remains unclear. Accordingly, the hypothesis that alterations in TGF-beta signaling occur during aneurysm formation was tested in a murine model of TAA.
Methods:
TAAs were surgically induced in mice (C57BL/6J) and aortas were analyzed at predetermined time points (1, 2, and 4 weeks post-TAA induction). Quantitative real-time PCR (QPCR) was performed to evaluate the expression of 84 relevant TGF-beta superfamily genes, and the protein levels of key signaling intermediates were measured by immunoblotting. Results were compared to unoperated reference control mice.
Results:
QPCR revealed increased expression of TGF-beta superfamily ligands (Gdf-2, -6, -7, Inhba), ligand inhibitors (Bmper, Chrd, Gsc), and transcriptional regulators (Dlx2, Evi1), among other genes (Cdkn2b, Igf1, IL-6). Protein levels of TGF-beta receptor(II), Smad2, Smad1/5/8, phospho-Smad1/5/8, and Smurf1 were increased from control values post-TAA induction. Both TGF-beta receptor(I) and Smad4 were decreased from control values, while ALK-1 levels remained unchanged.
Conclusions:
These alterations in the TGF-beta pathway suggest a mechanism by which primary signaling is switched from a TGF-betaR(I)/Smad2-dependent response, to an ALK-1/Smad1/5/8 response, representing a significant change in signaling outcome, which may enhance matrix degradation.
