Figure 6.

Infusion of Ang II in SM-Tfam^−/− mice predisposes mice to lethal aortic aneurysm and dissections. A, Experimental design: 56 days (8 weeks) after tamoxifen injections, Ang II minipumps were implanted in 6 SM-Tfam^+/+ and 10 SM-Tfam^−/− male mice. Ultrasound and blood pressure (BP) analysis was performed 6 times (empty triangles). B, Evolution of systolic and diastolic BP (top) and maximal AsAo and AbAo diameters (bottom) on Ang II infusion. C, Representative aortic ultrasound images after 28 days of Ang II infusion in SM-Tfam^+/+ and SM-Tfam^−/− mice. Discontinuous red lines mark the lumen boundary and discontinuous yellow lines and arrows denote the lumen diameter. D, Representative macroscopic images of aortas from the same animal cohort shown in A. Red arrowheads indicate aneurysms, dissections, and intramural hematomas. E, Aortic aneurysm incidence and percent survival of Ang II−infused SM-Tfam^+/+ and SM-Tfam^−/− mice from the same cohort shown in A. F, Incidence and localization of lethal aortic dissections and IMH in the same cohort shown in A. G, Representative histologic analysis on sections of AsAo, TDAo, and AbAo from the same cohort shown in A. Statistical significance was assessed by mixed-effects linear model (B) and log-rank (Mantel–Cox) test (E). Data are mean±SEM. Red arrows indicate intramural hematomas. *False lumen; P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs. SM-Tfam^+/+ mice. AbAo indicates abdominal aorta; Alcian B, Alcian blue; AngII, angiotensin II; AsAo, ascending aorta; BP, blood pressure; EVG, elastin Van Gienson; H/E, hematoxylin eosin; IMH, intramural hematomas; Masson T, Masson’s trichrome; MFS, Marfan syndrome; NR, nicotinamide riboside; SM-Tfam^+/+, tamoxifen–treated Myh11-Cre^ERT2Tfam^Wt/Wt mice; SM-Tfam^−/−, tamoxifen–treated Myh11-Cre^ERT2Tfam^flox/flox mice; TDAo, thoracic descending aorta; Tfam, mitochondrial transcription factor A; Tmx, tamoxifen; TorAo, Thoracic aorta; and TorAo/AbAo, Thoracic/Abdominal aorta.