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La legumaína es un modulador endógeno de la integrina αvβ3 que desencadena la degeneración, disección y ruptura

Lihong Pan^1,2,3, Peiyuan Bai^4,2,3, Xinyu Weng^4,2,3

¹Institutes of Biomedical Sciences, Fudan University, Shanghai, China (L.P., S.C., A.S., J.G.).

|January 31, 2022

Resumen

La legumaína (LGMN) promueve la disección aórtica torácica (TAD) al permitir la transformación de las células musculares lisas vasculares. La inhibición de LGMN en los macrófagos puede ofrecer una nueva estrategia terapéutica para la prevención y el tratamiento de la TA.

Área de la Ciencia:

Biología cardiovascular
La medicina molecular
Biología vascular

Sus antecedentes:

La disección aórtica torácica (TAD) implica la degradación de la matriz extracelular y el cambio fenotípico de las células musculares lisas vasculares (VSMC).
La legumaína (LGMN) está implicada en la degradación de la matriz extracelular, pero su papel en la diferenciación de VSMC y la patogénesis de TAD no está claro.

Objetivo del estudio:

Investigar el papel del LGMN en la diferenciación del CMV y su contribución a la disección de la aorta torácica (DAT).

Principales métodos:

Se han examinado los genes de expresión diferencial de los conjuntos de datos de microarrays públicos.
Se utilizaron ratones con knockout de Lgmn (incluidos los macrófagos específicos) y modelos de TAD inducidos por BAPN.
Se realizó secuenciación de ARN, ensayos de cocultivo celular, coinmunoprecipitación y análisis de colocalización.

Principales resultados:

La LGMN fue regulada al alza en aortas y sueros de pacientes con TAD y ratones.
La deficiencia o inhibición de Lgmn mejoró la progresión de TAD y la degradación de la matriz extracelular.
El LGMN derivado de los macrófagos inhibió la diferenciación del VSMC al interactuar con la integrina αvβ3, exacerbando el TAD.

Conclusiones:

La señalización de LGMN, particularmente de los macrófagos, juega un papel crítico en el desarrollo de TAD.
La orientación de LGMN presenta una nueva estrategia terapéutica potencial para la disección de la aorta torácica.

Palabras clave:

Las fosfohidrolasas GTP aneurisma, disección Matriz extracelular Las integrinas músculo, liso y vascular

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