Effects of the sodium-glucose cotransporter 2 inhibitors Canagliflozin, Dapagliflozin and Empagliflozin on endothelial barrier dysfunction : An in-vitro study

One of the most challenging tasks facing modern healthcare are cardiovascular diseases (CVDs), which are the leading cause of death around the world. That is why prevention, early detection, and optimal therapy of CVDs are extremely important for the medical care of the affected patients.  A key element of a healthy cardiovascular status is an intact endothelium which consists of a monolayer of endothelial cells and is in direct contact with the circulating blood. Therefore, the endothelium is permanently exposed to hemodynamic forces in the form of shear stress and repeated mechanical stress (RMS). Alterations in these forces directly affect the endothelium and can potentially activate destructive pathways. In combination with other cardiovascular risk factors, such as diabetes mellitus (DM), hypercholesterolemia, obesity, and excessive hemodynamic forces these alterations can ultimately result in CVDs.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), a recently approved class of diabetic drugs lowering blood sugar levels by inhibiting glucose reabsorption in the kidney, have shown beneficial effects beyond reducing the blood glucose level. Multiple independent clinical studies demonstrated that all SGLT2is decrease the risk of developing CVDs. However, the mechanisms behind these cardioprotective effects are still not fully elucidated.

The present study investigated the effects of the SGLT2is Empagliflozin (EMPA), Dapagliflozin (DAPA) and Canagliflozin (CANA) on human coronary artery endothelial cells (HCAECs) exposed to RMS which was applied by repeated stretching (RS) of the endothelial cell monolayer. Endothelial permeability, vascular endothelial cadherin (VE-cadherin) expression levels and ROS levels were determined after exposure to non-detrimental (5% RS) and detrimental RMS (10% RS) for 24h.


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