SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice

Male 0301 basic medicine Pulse Wave Analysis Actins Mice, Inbred C57BL Mice Oxidative Stress 03 medical and health sciences Diabetes Mellitus, Type 2 Sodium-Glucose Transporter 2 Animals Humans Original Article Vascular Diseases Sodium-Glucose Transporter 2 Inhibitors Aged
DOI: 10.1007/s11357-022-00563-x Publication Date: 2022-04-15T06:02:35Z
ABSTRACT
Abstract Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in pathogenesis cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors now known to decrease morbidity mortality type diabetes. However, whether SGLT2 inhibition attenuates vascular aging unknown. We first confirmed a cohort adult subjects that associated impaired function increased stiffness these variables are inversely correlated. Next, we investigated empagliflozin (Empa) ameliorates reduces aged mice dysfunction. Specifically, assessed mesenteric artery (via flow-mediated dilation pressure myography mechanical responses, respectively) aortic (in vivo via pulse wave velocity ex atomic force microscopy) Empa-treated (14 mg/kg/day for 6 weeks) control 80-week-old C57BL/6 J male mice. report exhibited improved compared control, parallel reduced stiffness. Additionally, had greater nitric oxide synthase activation, lower phosphorylated cofilin, filamentous actin content, downregulation pathways involved production reactive oxygen species. Our findings demonstrate Empa improves preclinical model aging, making potential therapeutic alternative reduce progression CVD older individuals. Graphical abstract
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