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Evaluation of the role of sodium-glucose co-transporters SGLT1 and 2 in the induction of endothelial senescence and dysfunction using an in vitro and in vivo approach

Abstract : Sodium-glucose cotransporter (SGLT)2 inhibitors have shown remarkable cardiovascular protective effects with reduced risk of cardiovascular mortality and hospitalization for heart failure in T2DM patients with a high cardiovascular risk and that this effect is independent of glucose control. The possibility that SGLT1 and 2 inhibitors protect the cardiovascular system by targeting the pivotal protective endothelial function remains unclear. The first in vitro study indicates that angiotensin II and circulating microparticles from patients with coronary artery disease via the activation of the local angiotensin system are potent inducers of SGLT1 and 2 expression to promote endothelial senescence and dysfunction. The second in vivo study indicates that the selective SGLT2 inhibitor empagliflozin protects the heart and the vascular system, and that the treatment is particularly effective to delay premature vascular senescence known to promote the development of cardiovascular diseases at arterial sites at risk of atherogenesis. Altogether, these studies suggest that inhibition of SGLT2 and/or SGLT1 might be an attractive therapeutic strategy to protect the endothelial function, and the subsequent development of cardiovascular diseases.
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Sin-Hee Park. Evaluation of the role of sodium-glucose co-transporters SGLT1 and 2 in the induction of endothelial senescence and dysfunction using an in vitro and in vivo approach. Pharmacology. Université de Strasbourg, 2019. English. ⟨NNT : 2019STRAJ041⟩. ⟨tel-02494023⟩

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