Impact of SGLT2i on Cardiac Remodeling and the Soleus Muscle of Infarcted Rats

Figure 1. Effects of SGLT2 inhibition on the soleus structural parameters. (A) Representative haematoxylin and eosin-stained histological sections. Bar: 50 µm; (B) soleus weight-to-body weight (BW) ratio; (C) cross-sectional area (CSA); (D) Frequency of the fibres according to CSA; (E,F) Type I and II myosin heavy chain (MyHC) isoforms; (G) Western blot representative blots of MyHC isoforms. Sham: control group (n = 5); Sham + EMPA: Sham treated with empagliflozin (EMPA; n = 6); MI: myocardial infarction (n = 7); MI + EMPA: MI treated with EMPA (n = 7). Data are means ± SD and individual values or relative frequency; ANOVA for a 2 × 2 factorial design and Tukey; p < 0.05: * vs. Sham; # vs. Sham + EMPA; † vs. MI.

Figure 2. Soleus muscle oxidative stress. (A,B) Concentration of oxidative stress markers malondialdehyde (MDA) and protein carbonylation; (C,D) maximum activity of antioxidant superoxide dismutase and catalase; (E,F) expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and Kelch-like ECH-associated protein 1 (Keap-1) evaluated by Western blot; (G) representative Western blots of Keap-1, Nrf-2, and GAPDH. Sham: control group (n = 5); Sham + EMPA: Sham treated with empagliflozin (EMPA; n = 6); MI: myocardial infarction (n = 7); MI + EMPA: MI treated with EMPA (n = 7). Data are the means ± SD and individual values; ANOVA for a 2 × 2 factorial design and Tukey; p < 0.05: * vs. Sham; † vs. MI.

Figure 3. Muscle energy metabolism. (A–C) Maximum activity of glycolysis pathway enzymes; (D) maximum activity of the citric acid cycle enzyme, citrate synthase; (E) maximum activity of beta-oxidation pathway enzyme, beta-hydroxyacyl dehydrogenase (BHADH). Sham: control group (n = 5); Sham + EMPA: Sham treated with empagliflozin (EMPA; n = 6); MI: myocardial infarction (n = 7); MI + EMPA: MI treated with EMPA (n = 7). Data are the means ± SD and individual values; ANOVA for a 2 × 2 factorial design and Tukey; p < 0.05: * vs. Sham; † vs. MI.

Figure 4. Mitochondrial respiratory complex expressions evaluated by Western blot. (A–E) Protein expression of oxidative phosphorylation complexes; (F) protein expression of peroxisomal proliferators-activated receptor γ-coactivator-1α (PGC-1α); (G) representative gels. Sham: control group (n = 5); Sham + EMPA: Sham treated with empagliflozin (EMPA; n = 6); MI: myocardial infarction (n = 7); MI + EMPA: MI treated with EMPA (n = 7). Data are the means ± SD and individual values; ANOVA for a 2 × 2 factorial design and Tukey; p < 0.05: * vs. Sham; # vs. Sham + EMPA; † vs. MI.

Figure 5. Protein expression evaluated by Western blot. (A–H) Protein expression of the anabolic IGF-1 pathway; (I–L) protein expression of the catabolic IGF-1 pathway; (M) representative blots. IGF-1: insulin-like growth factor Type 1; IGF-1R: IGF-1 receptor; Akt: protein kinase B; mTOR: mammalian target of rapamycin; p70S6K: ribosomal protein S6 kinase beta-1; FoxO3: forkhead box O3; MuRF-1: muscle RING-finger protein-1; MAFbx: muscle atrophy F-box. Sham: control group (n = 5); Sham + EMPA: Sham treated with empagliflozin (EMPA; n = 6); MI: myocardial infarction (n = 7); MI + EMPA: MI treated with EMPA (n = 7). Data are the means ± SD and individual values; ANOVA for a 2 × 2 factorial design and Tukey; p < 0.05: * vs. Sham; # vs. Sham + EMPA; † vs. MI.