Triiodothyronine protects infarcted myocardium by reducing apoptosis and preserving mitochondria

Fig. 1. T3 administration limits left ventricle (LV) failure. A Left ventricle sections of mice with cryo-infarction treated either with vehicle or T3 stained with Masson's trichrome revealing fibrosis in the cryo-infarcted area. Treatment with T3 strongly reduced scar area. B Percentage of LV area occupied by scar. C–E Quantification of cardiac function parameters obtained by echocardiographic analyses. C Ejection fraction % calculated with the Simpson equation, D systolic velocity of posterior wall (SVPW) evaluated by analyses of M-mode images, and E left ventricular internal diameter at end-systolic phase (LVIDs). F Representative images of M-mode analyses of sham-operated mice, vehicle-treated mice and 2xT3-treated mice. Data are expressed as mean ± SD, one-way ANOVA corrected with Tukey’s post hoc test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Scale bar: 500 μm

Fig. 2. Acute T3 treatment counteracts pathological LV remodeling limiting early cardiomyocyte apoptosis without promoting cardiomyocytes proliferation. A–C LV remodeling 28 days after cryoinjury. Quantification of A Feret’s diameter in cardiomyocytes and B cardiomyocyte area. C Representative images of cardiomyocytes morphology in sham control, vehicle-, and T3-treated mice 28 days after cryoinjury, tissues were stained with rhodamine-labeled WGA lectin (red), nuclei were stained with DAPI (blue). D Representative images of BrdU+ cells (green) in LV of mice 28 days after cryoinjury. Tissues were stained with LCA lectin (white), and nuclei were stained with DAPI (blue). Insets show enlarged images of proliferating positive cells. E, F Representative micrographs and corresponding quantification of apoptotic Tunel+ cells (green) in vehicle- and T3-treated mice 2 days and 7 days after cryoinjury, respectively. Tissues were stained with LCA lectin (white), and nuclei were stained with DAPI (blue). Insets show enlarged images of apoptotic cardiomyocytes. Data are expressed as mean ± SD, Student’s t-test or one-way ANOVA corrected with Tukey’s post hoc test. *p < 0.05, **p < 0.01. Scale bar:…

Fig. 3. High doses of T3 counteract long-term metabolic reprogramming of LV and restore mitochondria activity. Metabolites quantification in n = 3 vehicle- and T3-treated mice at A 2 days, B 7 days, and C 28 days following cryo-infarction (multiple unpaired t-test and Bonferroni Correction, p < 0.05). D Heatmap of the 13 quantified long-chain acylcarnitine in LV tissue of sham, vehicle-, and T3-treated mice at 7 and 28 days after cryoinjury. E Representative images and corresponding quantification of succinate dehydrogenase activity evaluated by the SDH activity assay (blue) in the LV of sham control (n = 3), vehicle-treated (n = 4), and T3-treated (n = 4) mice 28 days after cryo-infarction. Metabolites are presented with canonical abbreviation, and treatment groups are identified at the bottom of the plot. Data are expressed as mean ± SD, one-way ANOVA corrected with Tukey’s post hoc test. *p < 0.05. Scale bar: 20 μm