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, Griñán, Raquel, Mallen, Adrián, Navarro, Estanis, Purqueras, Elvira, Gomà, Montse, Sbraga, Fabrizio, Blasco Lucas, Arnau, Revilla, Giovanna, Santos, David, Canyelles, Marina, Julve, Josep, Escolà Gil, Joan Carles, Rotllan, Noemi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182931
Acceso en línea:https://hdl.handle.net/2445/182931
Access Level:acceso abierto
Palabra clave:Macròfags
Colesterol
Artèries coronàries
Malalties coronàries
Macrophages
Cholesterol
Coronary arteries
Coronary diseases
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 alpha-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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