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Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways: Experimental and clinical evidence.
Sanz, Raúl Lelio; García Menéndez, Sebastián; Inserra, Felipe; Ferder, Leon; Manucha, Walter.
Afiliación
  • Sanz RL; Department of Pathology, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
  • García Menéndez S; Department of Pathology, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
  • Inserra F; Department of Pharmacology, Instituto de Medicina y Biología Experimental de Cuyo, Centro Científico Tecnológico, Mendoza 5500, Argentina.
  • Ferder L; Department of Nephrology, Universidad de Maimónides, Ciudad Autónoma de Buenos Aires C1405, Argentina.
  • Manucha W; Department of Cardiology, Universidad de Maimónides, Ciudad Autónoma de Buenos Aires C1405, Argentina.
World J Exp Med ; 14(2): 91519, 2024 Jun 20.
Article en En | MEDLINE | ID: mdl-38948421
ABSTRACT
Mitochondrial dysfunction is a key driver of cardiovascular disease (CVD) in metabolic syndrome and diabetes. This dysfunction promotes the production of reactive oxygen species (ROS), which cause oxidative stress and inflammation. Angiotensin II, the main mediator of the renin-angiotensin-aldosterone system, also contributes to CVD by promoting ROS production. Reduced activity of sirtuins (SIRTs), a family of proteins that regulate cellular metabolism, also worsens oxidative stress. Reduction of energy production by mitochondria is a common feature of all metabolic disorders. High SIRT levels and 5' adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta, which promotes ketosis. Ketosis, in turn, increases autophagy and mitophagy, processes that clear cells of debris and protect against damage. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of drugs used to treat type 2 diabetes, have a beneficial effect on these mechanisms. Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events. SGLT2i also increase mitochondrial efficiency, reduce oxidative stress and inflammation, and strengthen tissues. These findings suggest that SGLT2i hold great potential for the treatment of CVD. Furthermore, they are proposed as anti-aging drugs; however, rigorous research is needed to validate these preliminary findings.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: World J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: World J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Estados Unidos