The sodium-dependent glucose transporters (SGLT) as a new promising pharmacological target in human ischaemic hearts

Background and aims: Recently, EMPAREG OUTCOME trial has shown that empagliflozin reduces cardiovascular mortality and the rate of hospitalization for heart failure, in patients with type 2 diabetes with previous cardiovascular events. The mechanisms underlying the cardioprotective effects of this sodium/glucose transporter 2 (SGT2) inhibitor are still unknown, though a direct action of the drug on the cardiomyocytes could be hypothesized. Materials and methods: We evaluated the expression of SGLT1 and SGLT2 by quantitative-real time-RT-PCR and western blot analyses, in tissue biopsies of healthy, ischemic and hypertrophic human hearts. Results: In this study, we evaluated the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in tissue biopsies of healthy (n=9), ischemic (n=9) and hypertrophic (n=6) human hearts. We found no expression of SGLT2 in either normal or pathological conditions, whereas SGLT1 was expressed in normal myocardial tissue and was significantly upregulated in ischemia and hypertrophy, in association with increased phosphorylation in activating domains of the intracellular secondmessengers AMP-activated protein kinase (AMPK), extracellular-signal regulated kinase 1 and 2 (ERK-1/2) and mammalian target of rapamycin (mTOR). Conclusion: Our findings suggest that the hyper-expression of SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection.