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
AUTHORS (13)
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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