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RETRACTED: Bartlett et al. Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models. <i>Int. J. Mol. Sci.</i> 2018, <i>19</i>, 2685.

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La señalización de la Na/K-ATPasa en los adipocitos promueve la aterosclerosis

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    La señalización de los adipocitos Na/K-ATPasa (NKA) con Adipo-NaKtide redujo significativamente la aterosclerosis en ratones. Este enfoque también mejoró la salud metabólica y redujo la inflamación, destacando el NKA como un objetivo terapéutico para la enfermedad cardiometabólica.

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    Área de la Ciencia:

    • Investigación cardiovascular
    • Enfermedad metabólica
    • Señalización celular

    Sus antecedentes:

    • La disfunción de los adipocitos, el estrés oxidativo y la inflamación están relacionados con trastornos metabólicos y aterosclerosis.
    • La señalización de la Na/K-ATPasa (NKA) α1 activa las cinasas Src, promoviendo el estrés oxidativo y la inflamación.
    • NaKtide, un inhibidor de NKA, reduce el estrés oxidativo sistémico y la inflamación in vivo.

    Objetivo del estudio:

    • Investigar el papel de la señalización NKA específica de los adipocitos en la aterosclerosis.
    • Evaluar el potencial terapéutico de la NKA dirigida a los adipocitos en un modelo de aterosclerosis en ratones.

    Principales métodos:

    • Inhibición de la NKA específica de los adipocitos mediante el uso de Adipo-NaKtide administrado a través de un vector lentiviral en ratones Apoe-/.
    • Inducción de la aterosclerosis con una dieta occidental durante 12 semanas.
    • Evaluación de la carga de la placa aterosclerótica, los marcadores inflamatorios y el estrés oxidativo en el tejido adiposo y el plasma.

    Principales resultados:

    • Adipo-NaKtide redujo significativamente el área de la placa aterosclerótica en el arco aórtico y el seno.
    • Disminución del contenido de macrófagos y células musculares lisas dentro de las lesiones ateroscleróticas.
    • Reducción de la inflamación del tejido adiposo, estrés oxidativo, mejor tolerancia a la glucosa y disminución de la inflamación sistémica.

    Conclusiones:

    • La señalización NKA de los adipocitos juega un papel crítico en el desarrollo de la aterosclerosis.
    • El tejido adiposo influye en la aterogénesis a través de mecanismos endocrinos y/o paracrinos.
    • La orientación hacia el NKA representa una estrategia terapéutica potencial para las enfermedades cardiometabólicas.