Gliflozin drug class and its effect on the proteome of cardiomyocytes

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. In my project I aim to identify the not yet understood mechanisms leading to the observed cardioprotective effects. In a first experiment I applied redox-proteomics to check if the drugs show antioxidative effects on a differentiated, human cardiomyocyte cell line (AC16) by mimicking disruption of oxygen supply (similar to heart failure): 1% oxygen (hypoxia), 21% oxygen (Control) and reperfusion injury (1% followed by re-oxygenation at 21% oxygen), as oxidative stress is one potential cause of heart failure.