Figure 9. Degradative SMCs exacerbate TAAD in a murine model of Marfan syndrome.

Tsc1^fl/fl Myh11-CreER^T2 mT/mG (Tsc1^fl/fl) and Fbn1^C1039G/+ Tsc1^fl/fl Myh11-CreER^T2 mT/mG (Fbn1^C>G Tsc1^fl/fl) mice were treated with tamoxifen (Tmx) or vehicle (Veh) at 1.5 weeks of age and their thoracic aortas examined at 12 weeks. (A) Ultrasound examination of ascending aortas (blue line) and measurements of in vivo diameter and distension (n = 5–17). (B) In situ examination of ascending (Asc) and descending (Desc) aortas (scale bar: 2 mm) showing aneurysm (black arrow) and dissection (white arrow). (C) Survival of Fbn1^C>G Tsc1^fl/fl mice treated with tamoxifen or vehicle (n = 17–18) and (D) hemopericardium (arrows) in animal with premature death. (E) mTOR signaling in thoracic aortas of tamoxifen-treated mice by Western blot and expression of phospho-S6 and S6 relative to HSP90 (n = 4). (F) Flow cytometry for LAMP2 (Mac-3) and GAL3 (Mac-2) expression by GFP⁺ SMCs in tamoxifen-treated mice (n = 3–6). Data are represented as individual values with mean ± SEM bars. *P < 0.05; **P < 0.01; ***P < 0.001 by 2‑way ANOVA (A and E), log-rank test (C), or t test (F).