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

• Published in: Biomedicine & pharmacotherapy 2022-02, Vol.146, p.112596-112596, Article 112596
• Main Authors: Hueso, Miguel, Griñán, Raquel, Mallen, Adrián, Navarro, Estanislao, Purqueras, Elvira, Gomá, Montse, Sbraga, Fabrizio, Blasco-Lucas, Arnau, Revilla, Giovanna, Santos, David, Canyelles, Marina, Julve, Josep, Escolà-Gil, Joan Carles, Rotllan, Noemi
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport; Cholesterol efflux; Cholesterol, HDL - genetics; Cholesterol, HDL - metabolism; Coronary artery disease; Down-Regulation; Humans; Macrophage; Macrophages - metabolism; Mice; MicroRNA; MicroRNAs - metabolism; MiR-125b; Receptors, Scavenger - metabolism; Reverse cholesterol transport; Scavenger receptor class B type 1 (SRB1); Vascular smooth muscle cell
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112596

To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). 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. 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. [Display omitted] •miR-125b is expressed in the aortic macrophages and vascular smooth muscle cells of patients with coronary artery disease.•miR-125b downregulates macrophage and smooth muscle cell scavenger receptor SR-B1 and cholesterol efflux to α-HDL.•miR-125b impairs the entire macrophage-specific reverse cholesterol transport rate.