Hueso, MiguelGriñán, RaquelMallen, AdriánNavarro, EstanisPurqueras, ElviraGomà, MontseSbraga, FabrizioBlasco Lucas, ArnauRevilla, GiovannaSantos, DavidCanyelles, MarinaJulve, JosepEscolà Gil, Joan CarlesRotllan, Noemi2022-02-042022-02-042022-02-01https://hdl.handle.net/2445/182931Objective: 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.3 p.application/pdfengcc by (c) Hueso, Miguel et al., 2021http://creativecommons.org/licenses/by/3.0/es/MacròfagsColesterolArtèries coronàriesMalalties coronàriesMacrophagesCholesterolCoronary arteriesCoronary diseasesinfo:eu-repo/semantics/article2022-02-03info:eu-repo/semantics/openAccess