Biomedicine & Pharmacotherapy (Feb 2022)

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

  • Miguel Hueso,
  • Raquel Griñán,
  • Adrián Mallen,
  • Estanislao Navarro,
  • Elvira Purqueras,
  • Montse Gomá,
  • Fabrizio Sbraga,
  • Arnau Blasco-Lucas,
  • Giovanna Revilla,
  • David Santos,
  • Marina Canyelles,
  • Josep Julve,
  • Joan Carles Escolà-Gil,
  • Noemi Rotllan

Journal volume & issue
Vol. 146
p. 112596

Abstract

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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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