The SGLT-2 Inhibitor Empagliflozin Improves Myocardial Strain, Reduces Cardiac Fibrosis and Pro-Inflammatory Cytokines in Non-Diabetic Mice Treated With Doxorubicin
Abstract
Abstract BackgroundEmpagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2, reduced the risk of hospitalization for heart failure and cardiovascular death in type 2 diabetic patients in the EMPA‐REG OUTCOME trial. Other clinical trials evaluated beneficial effects of empagliflozin in non-diabetic patients. We aimed to evaluate the effects of empagliflozin on myocardial strain of non-diabetic mice treated with doxorubicin evaluating changes in cardiac cytokine profile, fibrosis and apoptosis. Methods Preliminary cellular studies were performed on HL-1 human cardiomyocytes exposed to doxorubicin alone or combined to empagliflozin. Reactive oxygen species, intracellular calcium homeostasis, expression of leukotrienes, NF-kB and interleukin-1β, 8 and 6 were analysed. C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin (DOXO, n=6), empagliflozin (EMPA, n=6) or doxorubicin and empagliflozin (DOXO-EMPA, n=6). Radial and longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100). Cardiac fibrosis and apoptosis were studied through Picrosirius red and TdT-mediated dUTP nick-end labelling (TUNEL) assay, respectively; interleukins were quantified in tissues through ELISA.ResultsA significant increase in intracellular calcium and pro-inflammatory markers associated to pro-oxidant mediators were seen after cell exposure to doxorubicin; co-incubation with empagliflozin reduced significantly the magnitude of…
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