Unraveling cardiovascular benefits of sodium glucose co-transporter 2 inhibitors Focus on the endothelium

The aim of this thesis was to explore the underlying mechanisms behind the reduced cardiovascular risk observed by treatment with sodium glucose co-transporter 2 inhibitors (SGLT2i’s), with an emphasis on the direct effect of SGLT2i’s on endothelial dysfunction. endothelial protection of SGLT2i’s.
We firstly reviewed pathological mechanisms and potential treatments for the disturbed coagulation and haemostasis in patients with D. We then summarized the progressions and limitations in preclinical studies exploring the effects of SGLT2i’s on ECs, to give more insight into the promising cardiovascular benefit of these drugs. Next, we investigated the underlying mechanism behind the ROS reduction capacity of SGLT2i’s in human ECs stimulated with TNF-α and mechanical forces (stretch and flow). Finally, we evaluated the potential risks and benefits of SGLT2i’s administration during the perioperative period: by collecting blood samples from an ongoing clinical study in which patients undergoing cardiac surgery with cardiopulmonary bypass received EMPA during the perioperative period. We tested whether EMPA treatment will prevent surgery-related cardiovascular injury as determined by troponine release.
In summary, the present thesis showed that SGLT2i’s exerted profound endothelial protective effect on ECs exposed to the pro-inflammatory cytokine TNF-α and disturbed mechanical forces. Morover we unraveld parts of the underlying mechanisms underlying these effects. However, it is still challenging to translate the findings from cellular experiments to patients undergoing cardiac surgery.