El tratamiento oral con metformina previene signos tempranos de arterioesclerosis aórtica inducida por AGE/RAGE en ratas con síndrome metabólico
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Introducción: el síndrome metabólico (SM) se asocia al aumento de estrés carbonílico y productos de glicación avanzada (AGE) y favorece la calcificación arterial (CA) por transdiferenciación osteogénica de células de músculo liso vascular (CMLV). La metformina (MET) inhibe esa transdiferenciación in vitro. Evaluamos si MET oral previene CA en un modelo experimental de SM.
Materiales y métodos: ratas Wistar macho jóvenes adultos fueron separadas en dos grupos: uno recibió agua como bebida (C) y el otro una solución 20% de fructosa (F). Tras dos semanas, y por cuatro más, cada grupo original se dividió, agregándose MET (100 mg/kg/día) a la bebida de la mitad de cada grupo (así, M y FM). Se midieron parámetros metabólicos y corporales. La aorta se disecó para análisis histomorfométrico e inmunohistoquímico. Se aislaron CMLV aórticas para evaluar la actividad de fosfatasa alcalina (FAL), producción de colágeno, mineralización extracelular y expresión génica de Runx2 y receptor para AGE (RAGE).
Resultados: el grupo F desarrolló rasgos compatibles con SM: mayor adiposidad, hiperglucemia, dislipemia y aumento de fructosamina. Las aortas de F evidenciaron reducción de la relación capa elástica/muscular, aumento de colágeno, acumulación de AGE y sobreexpresión de RAGE. Las CMLV de F mostraron mayor actividad FAL, incremento de colágeno y mineralización, junto a aumento de expresión de Runx2 y RAGE. El cotratamiento con MET previno estas alteraciones. In vitro, MET bloqueó la inducción de RAGE por AGE; efecto que se anuló con un inhibidor de la proteína quinasa activada por AMP (AMPK).
Conclusión: estos resultados indican que MET atenúa la glicación extracelular, la activación AGE/RAGE y el remodelado vascular asociado al SM experimental.
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