In vivo inhibition of miR-125b-5p modulates monocyte trafficking through the CCR7 receptor and reduces atherosclerosis
Monocytes and regulatory noncoding RNAs play a crucial role in the development of atherosclerosis (ATH). We have previously shown that miR-125b-5p was upregulated in aortic macrophages, and the aim of this paper was to further study the "in vivo" impact of miR-125b-5p in ATH progression. E...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p21092 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21092 |
| Access Level: | acceso abierto |
| Palabra clave: | atherosclerosis CCR7 macrophages miR-125b-5p miRNAs |
| Sumario: | Monocytes and regulatory noncoding RNAs play a crucial role in the development of atherosclerosis (ATH). We have previously shown that miR-125b-5p was upregulated in aortic macrophages, and the aim of this paper was to further study the "in vivo" impact of miR-125b-5p in ATH progression. Eight-weeks-old ApoE(-/-) mice, fed with a high-fat diet for 14 wk, were treated with a miR-125b-5p mimic, with its specific antagonist (antagomiR-125b), with a control scrambled sequence (control oligonucleotide SC) or with a control vehicle with phosphate-buffered saline (PBS) for 4 wk. Treatment with the miR-125b-5p mimic increased plaque sizes, macrophage infiltration, and NF-kappa B activation compared to PBS control, independently of cholesterol levels. In contrast, treatment with a specific antagomir produced opposite effects and increased the number of M2 macrophages. Finally, the miR-125b-5p mimic was found to reduce expression of the chemokine receptor CCR7 in the human monocyte cell line THP-1 cells, and the mouse macrophage-like cell line RAW264.7 cells, as well as in the aortas and livers of mice, whereas the antagomiR-125b increased CCR7 expression. Reduced CCR7 expression was also observed in the aorta of patients with coronary artery disease. miR-125b-5p mimic increased inflammation and ATH progression. Targeting miR-125b-5p with a specific antagomir reduced plaque size and macrophage infiltration and increased expression of the chemokine receptor CCR7. These results support a role for miR-125b-5p in the upregulation of CCR7 expression and monocyte trafficking, thus restricting vascular inflammation in ATH progression. |
|---|