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SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice.
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.
Afiliação
  • Soares RN; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Ramirez-Perez FI; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Cabral-Amador FJ; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Morales-Quinones M; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Foote CA; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
  • Ghiarone T; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Sharma N; Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Power G; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
  • Smith JA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
  • Rector RS; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
  • Martinez-Lemus LA; Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
  • Padilla J; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, MO, USA.
  • Manrique-Acevedo C; Department of Medicine, University of Missouri, Columbia, MO, USA.
Geroscience ; 44(3): 1657-1675, 2022 06.
Article em En | MEDLINE | ID: mdl-35426600
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Diabetes Mellitus Tipo 2 / Inibidores do Transportador 2 de Sódio-Glicose Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Animals / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Diabetes Mellitus Tipo 2 / Inibidores do Transportador 2 de Sódio-Glicose Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Animals / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article