Investigating the cardioprotective effects of SGLT-2 inhibitors

Abstract

Beyond their initial approvement for treating diabetic conditions, Sodium-Glucose co-transporter 2 (SGLT-2) inhibitors have recently been found to also offer cardioprotective properties. Since cardiovascular problems are one of the major complications that diabetic patients face, this finding was groundbreaking. Meanwhile it was shown that the cardioprotective effects are not limited to diabetic patients and the inhibitors" approvements have been expanded respectively. Observations from clinical studies hint in the direction that those effects exceed the glucose lowering effect without offering an explanation for the underlying mechanisms. Since the drug"s target protein SGLT-2 is exclusively expressed in the early proximal tubule where it is responsible for the reabsorption of glucose it remains inconclusive why the positive effects are observed in the heart. To identify off-targets of the drug, thermal proteome profiling is applied. In this method the basic principle is that the thermal stability of proteins is increased when binding to the drug, reflected by an increased stability of the respective protein when applying a temperature gradient. In order to target the off targets in the cardiac environment those experiments are carried out in the human cardiac cell line AC16 (cardiomyocytes derived from left ventricular heart tissue).