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El receptor olfativo 2 en los macrófagos vasculares impulsa la aterosclerosis por la producción de IL-1 dependiente
Marco Orecchioni1, Kouji Kobiyama1,2, Holger Winkels1,3
1La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|January 13, 2022
Resumen
Este estudio revela que los receptores olfativos (OLFR) como el Olfr2 en los macrófagos detectan el octanal, un producto de la peroxidación lipídica. Dirigirse a estos receptores puede ofrecer una nueva estrategia terapéutica para la aterosclerosis.
Área de la Ciencia:
- Biología cardiovascular
- Inmunología
- Biología sensorial
Sus antecedentes:
- La aterosclerosis es una enfermedad arterial inflamatoria que afecta a los macrófagos.
- Los receptores olfativos (OLFR) son quimiorreceptores acoplados a proteínas G que son cruciales para el olfato.
Objetivo del estudio:
- Investigar el papel de los receptores olfativos en los macrófagos vasculares y su posible participación en la aterosclerosis.
Principales métodos:
- Análisis de la expresión del receptor olfativo Olfr2 en los macrófagos vasculares del ratón.
- Evaluación del efecto del octanal en la activación del inflamatorio NLRP3 y la secreción de IL-1β.
- Evaluación del impacto de los niveles octanales y la orientación Olfr2 en la aterosclerosis en modelos de ratón.
Principales resultados:
- Los macrófagos vasculares de ratón expresan Olfr2 y las moléculas de señalización asociadas.
- Octanal activa el inflamatorio NLRP3 y la secreción de interleucina-1β en los macrófagos.
- La elevación octanal empeoró la aterosclerosis, mientras que la inhibición genética de Olfr2 redujo las placas ateroscleróticas.
Conclusiones:
- El receptor olfativo Olfr2 detecta el octanal, un producto de la peroxidación lipídica que se encuentra en el plasma sanguíneo.
- La activación de Olfr2 contribuye al desarrollo de la aterosclerosis.
- La inhibición del receptor olfativo 6A2 (OR6A2) presenta una vía terapéutica potencial para la aterosclerosis.
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