MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport

Objective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vasc...

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Detalles Bibliográficos
Autores: Hueso, Miguel|||0000-0002-1824-9141, Griñán, Raquel|||0000-0002-9457-3365, Mallen, Adrián, Navarro, Estanislao, Purqueras, Elvira, Gomà-Gállego, Montserrat, Sbraga, Fabrizio, Blasco-Lucas, Arnau|||0000-0002-2796-7428, Revilla, Giovanna|||0000-0003-2971-5651, Santos, David|||0000-0003-1157-4969, Canyelles, Marina|||0000-0002-0278-5337, Julve i Gil, Josep|||0000-0002-6531-2246, Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Rotllan, Noemi|||0000-0002-0587-8045
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282279
Acceso en línea:https://ddd.uab.cat/record/282279
https://dx.doi.org/urn:doi:10.1016/j.biopha.2021.112596
Access Level:acceso abierto
Palabra clave:Cholesterol efflux
Reverse cholesterol transport
Scavenger receptor class B type 1 (SRB1)
MicroRNA
MiR-125b
Macrophage
Vascular smooth muscle cell
Coronary artery disease
Descripción
Sumario:Objective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vascular smooth muscle cells (VSMCs). We identified SCARB1 as a direct target of miR-125b by repressing the activity of the SCARB1 3'-untranslated region reporter construct. Moreover, the overexpression of miR-125b in both human and mouse macrophages as well as VSMCs was found to downregulated the expression of the SCARB1 and the SR-B1 protein levels, thereby impairing α-HDL-mediated macrophage cholesterol efflux in vitro. The in vivo reverse cholesterol transport (RCT) rate from non-cholesterol-loaded macrophages transfected with miR-125b to feces was also found to be decreased when compared with that of control mimic-transfected macrophages. Conclusions: Together, these results provide evidence that miR-125b downregulates SCARB1 and SR-B1 in both human and mouse macrophages as well as VSMCs, thereby impairing macrophage cholesterol efflux in vitro and the whole macrophage-specific RCT pathway in vivo.

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