Effects of Empagliflozin on the Proteome of Cardiac Cells

Abstract

Death from cardiovascular (CV) diseases is the most relevant macrovascular complication in type 2 diabetes. A new drug class that offers cardioprotective properties are sodium-glucose co-transporter-2 (SGLT-2) inhibitors, initially used for the treatment of type 2 diabetes. Meanwhile trials have shown that these properties are beyond the effect of lowering glucose concentrations in the blood. Therefore, their application in non-diabetic patients suffering from heart diseases has recently been approved. Even though cardiovascular events as heart failure are multicausal, the disbalance in reactive oxygen species (ROS) and antioxidant potential of the tissue also defined as oxidative stress is one relevant aspect in the development of heart failure. As Empagliflozin is reported to exhibit antioxidative effect in cardiac tissue, our goal was to unravel the underlying mechanism. To that end differentiated, human cardiomyocyte cell line (AC-16) was treated with Empagliflozin in a setting mimicking reperfusion injury (1% oxygen followed by re-oxygenation at 21% oxygen). A similar experimental setup was done in stem-cell derived cardioids to increase the translational aspect. Quantitative and redox proteomic methods are applied, to monitor the influence of the drugs at the different oxygen availabilities. As a measure of oxidative stress, the levels of reduced and oxidized antioxidant Glutathione (GSH) levels were further determined.