Fig. 2
From: Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism
Inhibition of cardiac mitochondrial AKT1 signaling led to development of cardiomyopathy and mitochondrial dysfunction. A Left, representative images of trichrome stained myocardial sections. TAM or CO was administered once as indicated. 7 days after injection, cardiac fibrosis was quantified by trichrome staining. Scale bar = 100 μm. Right, quantification of cardiac fibrosis (n = 12 (TAM-Myh6-Cre), n = 9 (TAM-MDNAKT), n = 10 (CO-CAMDAKT), n = 8 (TAM-CAMDAKT); p < 0.0001). B Cardiac left ventricular septum thickness, posterior wall thickness and ventricular mass were analyzed by echocardiogram 7 days after TAM or CO injection in CAMDAKT mice. LV Mass is given as a relative percent of total heart mass. (n = 14 (CO), n = 15 (TAM); p < 0.001, < 0.05, < 0.001). C Cardiac function was measured by echocardiogram 7 days after TAM or CO injection in CAMDAKT mice. Left ventricular fractional shortening, ejection fraction and velocity of circumferential fiber shortening were quantified (n = 14 (CO), n = 15 (TAM); p < 0.001, < 0.001, < 0.0001). D Mitochondrial DNA were analyzed by RT-qPCR and presented as a ratio of mitochondrial DNA to nuclear DNA fold change relative to CO-CAMDAKT (n = 3 (CO), n = 3–6 (TAM); p < 0.05). E Expression of mitochondrial biogenesis markers PPARα and PGC1α were measured by RT-qPCR at timepoints post TAM or CO injection. Data are presented as relative fold change to CO-CAMDAKT (n = 3 per group; p < 0.05, < 0.05). F Representative graph of mitochondrial respiration, measured by Seahorse assay, 3 days after TAM or CO injection. G Basal respiration, stage 3 respiration, and proton leak in mitochondria were calculated. Myocardial mitochondria were isolated from TAM-wild type (n = 6), TAM–Myh6-Cre (n = 5), TAM-MDNAKT (n = 5), CO-CAMDAKT (n = 5) and TAM–CAMDAKT (n = 7) (p < 0.05, < 0.001, < 0.01). H ATP levels in CAMDAKT mitochondria from 1, 3 and 7-days post TAM or CO injection. ATP levels were quantified by mass spectrometry. Data are presented as relative levels to CO-CAMDAKT (n = 4–5 per group; p < 0.01, < 0.05)