Figure 3.

Cardiac ablation of MITOL caused heart failure with severe fibrosis

(A) Kaplan-Meier survival curve of wild-type (WT: gray line) and tamoxifen-treated Mitol^f/f;αMHC-Cre^Mer (MITOL cKO: black line) mice. Control = 25, MITOL cKO = 45 mice per group. ∗p < 0.05, Student’s t-test.

(B) Cardiac dysfunction in MITOL-cKO mice. Echocardiographic analysis of left ventricular dimensions and cardiac function in mice. FS, fractional shortening of left ventricular diameter, calculated as [(LVIDd – LVIDs)/LVIDd] × 100. LVIDs; systolic left ventricular internal diameters. LVIDd; diastolic left ventricular internal diameters. Mean ±SEM (n = 3). ∗p < 0.05, Student’s t-test.

(C) Representative M-mode echocardiograms from control and MITOL-cKO mice six months after tamoxifen treatment. Red arrow, LVIDs. Blue arrow, LVIDd.

(D and E) Cardiac hypertrophy in MITOL-cKO mice. Hearts from control and cKO mice were isolated and photographed six months after tamoxifen-treatment. Scale represents 1 mm (D). Heart-to-body and Lung-to-body weight ratio in control and cKO mice six months after tamoxifen treatment. Mean ±SEM (n = 6). Analysis was performed with two-way ANOVA followed by Bonferroni post hoc analysis. ∗∗p < 0.01. (E).

(F) Elevated levels of the hypertrophic markers in MITOL-cKO mice. The gene expression of αMHC and βMHC was analyzed by qRT-PCR. Bar graphs show the relative mRNA levels of αMHC and βMHC, and the ratio of βMHC to αMHC in MITOL-cKO mice compared with control mice. Mean ± SEM (n = 4). ∗∗∗p < 0.001., Student’s t-test.

(G and H) Myocardial fibrosis in MITOL-cKO mice. Representative views of cross-sections of control and MITOL-cKO mice three and six months after tamoxifen-treatment, stained with Masson’s trichrome to detect fibrosis (G). Bars, 100 μm. The fibrotic areas were measured (H). Mean ±SEM (n = 3). ∗∗p < 0.01. Representative low-magnification views of cross-sections at the midventricle from cKO mice three and six months after tamoxifen-treatment (bottom).