Soares 2022 Geroscience

Soares RN, Ramirez-Perez FI, Cabral-Amador FJ, Morales-Quinones M, Foote CA, Ghiarone T, Sharma N, Power G, Smith JA, Rector RS, Martinez-Lemus LA, Padilla J, Manrique-Acevedo C (2022) SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice. https://doi.org/10.1007/s11357-022-00563-x

» Geroscience 44:1657-75. PMID: 35426600 Open Access

Soares Rogerio N,  Ramirez-Perez Francisco I,  Cabral-Amador Francisco J,  Morales-Quinones Mariana, Foote Christopher A,  Ghiarone Thaysa,  Sharma Neekun,  Power Gavin,  Smith James A,  Rector R Scott,  Martinez-Lemus Luis A,  Padilla Jaume,  Manrique-Acevedo Camila (2022) Geroscience

Abstract: Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors is now known to decrease cardiovascular morbidity and mortality in type 2 diabetes. However, whether SGLT2 inhibition attenuates vascular aging is unknown. We first confirmed in a cohort of adult subjects that aging is associated with impaired endothelial function and increased arterial stiffness and that these two variables are inversely correlated. Next, we investigated whether SGLT2 inhibition with empagliflozin (Empa) ameliorates endothelial dysfunction and reduces arterial stiffness in aged mice with confirmed vascular dysfunction. Specifically, we assessed mesenteric artery endothelial function and stiffness (via flow-mediated dilation and pressure myography mechanical responses, respectively) and aortic stiffness (in vivo via pulse wave velocity and ex vivo via atomic force microscopy) in Empa-treated (14 mg/kg/day for 6 weeks) and control 80-week-old C57BL/6 J male mice. We report that Empa-treated mice exhibited improved mesenteric endothelial function compared with control, in parallel with reduced mesenteric artery and aortic stiffness. Additionally, Empa-treated mice had greater vascular endothelial nitric oxide synthase activation, lower phosphorylated cofilin, and filamentous actin content, with downregulation of pathways involved in production of reactive oxygen species. Our findings demonstrate that Empa improves endothelial function and reduces arterial stiffness in a preclinical model of aging, making SGLT2 inhibition a potential therapeutic alternative to reduce the progression of CVD in older individuals. • Keywords: Aging, Arterial stiffness, Endothelial function, Oxidative stress, SGLT2 • Bioblast editor: Plangger M • O2k-Network Lab: US MO Columbia Rector RS

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2022-11