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MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport 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 Macròfags Colesterol Artèries coronàries Malalties coronàries Macrophages Cholesterol Coronary arteries Coronary diseases 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. 2022-02-04T17:40:51Z 2022-02-04T17:40:51Z 2022-02-01 2022-02-03T10:29:03Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://hdl.handle.net/2445/182931 eng Reproducció del document publicat a: https://doi.org/10.1016/j.biopha.2021.112596 Biomedicine & Pharmacotherapy, 2022, vol. 146, p. 112596 https://doi.org/10.1016/j.biopha.2021.112596 cc by (c) Hueso, Miguel et al., 2021 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess 3 p. application/pdf Elsevier BV Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))