Sodium glucose transporter 2 inhibition reduces arterial stiffness and improves endothelial function in a mouse model of aging

Abstract

Aging of the vasculature is characterized by arterial stiffening and endothelial dysfunction, both key events in the pathogenesis of cardiovascular disease (CVD). Thus, novel strategies are urgently needed to prevent and ameliorate vascular aging. In this context, treatment with sodium glucose transporter 2 inhibitors (SGLT2i) is now known to decrease cardiovascular morbidity and mortality in subjects with type 2 diabetes, heart failure, and chronic kidney disease. However, whether SGLT2i attenuates aging-related arterial stiffening and endothelial dysfunction, thereby reducing CVD risk is unknown. Herein, we tested the hypothesis that treatment with SGLT2i (Empagliflozin) reduces arterial stiffness and endothelial dysfunction in aging. To test this hypothesis, we assessed aortic stiffness (in vivo via pulse-wave velocity and ex vivo via atomic force microscopy) and mesenteric artery stiffness and endothelial function (via pressure myography mechanical responses and flow-mediated dilation, respectively) in Empagliflozin -treated (14 mg/kg/day for 6 weeks) and control (standard chow diet) 80 week-old C57BL/6J male mice (n=9 per group). We report that the Empagliflozin -treated cohort exhibited reduced aortic and mesenteric artery stiffness (p<0.05) as well as improved mesenteric endothelial function (p<0.05) when compared with the control cohort. The current findings support the hypothesis that Empagliflozin reduces arterial stiffness and improves endothelial function in a preclinical model of aging, making SGLT2i a potential alternative to reduce the progression of CVD in older individuals. Further experiments aimed at identifying the mechanisms by which Empagliflozin exerts its vascular effects on this model of aging are underway.