Figure 6.

A: Echocardiographic analysis on 9-month-old Sm22-Cre^+/0;Smad5^fl/− (KO) and control female littermates (Ctrl). Significantly larger systolic left ventricle internal diameters (LVIDs) and diastolic left ventricle internal diameters (LVIDd) and significantly decreased fractional shortening (FS) are observed in Sm22-Cre^+/0;Smad5^fl/− females (n = 10) compared with control mice (n = 9). No difference was observed between Sm22-Cre^+/0;Smad5^fl/− males (n = 4) and control mice (n = 4). *P < 0.05. B: Laminin staining was performed on heart sections to measure the myocyte size. No difference was observed between control (Ctrl, A) and Sm22-Cre^+/0;Smad5^fl/− mice (KO, E). Masson’s trichrome staining on sections of hearts isolated from a control (B) and a Sm22-Cre^+/0;Smad5^fl/− (Sm22KO; F) female littermate revealing no interstitial fibrosis in mutant or control hearts. C and G: CD31 staining of ECs demonstrating comparable capillary density in control (C) and Sm22-Cre^+/0;Smad5^fl/− mice (G). D and H: Immunostaining for α-SMA showing positive staining in coronary arteries in hearts of control (D) and Sm22-Cre^+/0;Smad5^fl/− (H) littermates. C: A treadmill experiment was performed both on males and females. After 1 day of training on the treadmill, the running endurance of all mice was analyzed. The time (in seconds) of running until exhaustion was recorded for each mouse. Statistical analysis demonstrated that Sm22-Cre^+/0;Smad5^fl/− (KO) females performed significantly (P = 0.005) worse than control females (Ctrl) but no differences could be observed between both male genotypes (P = 0.4). Original magnifications: ×400 (A, C, E, G); ×200 (B, D, F, H).