Mechanism of action of the SGLT2 inhibitor empagliflozin on endothelial dysfunction : An in vitro study
Endothelial dysfunction is present in patients with type 2 diabetes mellitus (T2DM) and has been linked to cardiovascular disease (CVD), which is the leading cause of mortality in diabetes. T2DM is associated with vascular inflammation, and levels of tumour necrosis factor α (TNFα) are elevated in the plasma of patients with diabetes and obesity. Empagliflozin (EMPA) is a relatively new glucose-lowering drug that inhibits sodium-glucose cotransporter 2 in the proximal tubule of the kidney, resulting in increased glycosuria together with decreased plasma levels of glucose. Interestingly, in the EMPA-REG outcome trial, EMPA was also shown to reduce major adverse cardiovascular events when added to the standard care of patients with T2DM and established CVD. However, the underlying molecular mechanisms of the cardiovascular protection from EMPA are currently unclear. Specifically, it is unknown whether and how EMPA affects the endothelium. Therefore, the aims of the present study were to evaluate whether EMPA protects the endothelium from TNFα-induced injury and to investigate the underlying mechanisms.