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Pàgina inicial > Articles > Articles publicats > MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport |
Data: | 2022 |
Resum: | 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. |
Ajuts: | Ministerio de Ciencia, Innovación y Universidades PID2019-104367RB-100 Agencia Estatal de Investigación RYC-201722879 Instituto de Salud Carlos III PI18/01108 Instituto de Salud Carlos III CM20/00033 Instituto de Salud Carlos III PI17/00232 Instituto de Salud Carlos III CPII18/00004 |
Nota: | Altres ajuts: European Regional Development Fund (ERDF); Fundació La Marató de TV3 2016 (303/C/2016, 201602.30.31); CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM). |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Cholesterol efflux ; Reverse cholesterol transport ; Scavenger receptor class B type 1 (SRB1) ; MicroRNA ; MiR-125b ; Macrophage ; Vascular smooth muscle cell ; Coronary artery disease |
Publicat a: | Biomedicine & pharmacotherapy, Vol. 146 (february 2022) , p. 112596, ISSN 1950-6007 |
9 p, 4.2 MB |