Abstract Wed094: Empagliflozin Preserves Heart Function and Reshapes Proteomics/Metabolomics in Dystrophic Heart
Abstract
Background:
Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene that eliminate functional dystrophin, leading to progressive motor decline and life-threatening cardiorespiratory complications. We investigated the therapeutic potential of empagliflozin (EMPA), a sodium/glucose cotransporter-2 inhibitor, on cardiac function and its impact on myocardial proteomic and metabolomic profiles in DMD.
Methods:
Adult male mdx mice (12-14 weeks) and DMD
mdx
rats (14-16 weeks) received EMPA, 30 mg/kg/day for mice and 10 mg/kg/day for rats, via drinking water for 4 months. Age- and sex-matched C57BL/10J mice and Sprague Dawley rats served as controls. Echocardiography at baseline and 12 weeks measured left ventricular ejection fraction (LVEF), fractional shortening (FS), cardiac output, heart rate, and stroke volume. In DMD
mdx
rats, high-throughput proteomic and metabolomic analyses of left ventricular tissue were performed, followed by in-silico pathway and transcription factor evaluations.
Results:
Cardiac function was markedly declined in both model of DMD (In C57BL/10J mice, the left ventricular ejection fraction (LVEF) was 68 ± 6.3%, while in Sprague Dawley rats, it was 71±4.3%). Chronically EMPA treatment increased LVEF (66 ± 5.8% versus 53.0 ± 5.7% in vehicle-treated mdx mice) and improved fractional shortening and cardiac output (p≤0.05, respectively). Similarly, DMD
mdx
rats exhibited enhanced LVEF (72.8 ± 8.0% compared to 60.9 ± 5.8%…
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