In vivo inhibition of miR-125b-5p modulates monocyte trafficking through the CCR7 receptor and reduces atherosclerosis
Por:
Mallén, A, Rotllan, N, Griñán, R, Varela, C, Bertolino, E, Paloschi, V, Maegdefessel, L, Escolà-Gil, JC, Aran, JM, Sbraga, F, Blasco-Lucas, A, Torras, J, Navarro, E, Hueso, M
Publicada:
25 ene 2026
Resumen:
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.
Filiaciones:
Mallén, A:
Inst Invest Biomed Bellvitge IDIBELL, Nephrol & Renal Transplantat Grp, Translat Med Area, Lhospitalet De Llobregat, Spain
Germans Trias & Pujol Res Inst IGTP, REMAR Grp, Badalona, Spain
Rotllan, N:
Inst Recerca St Pau Ctr CERCA, Barcelona, Spain
CIBER Diabet & Enfermedades Metab Asociadas, Barcelona, Spain
Griñán, R:
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain
Varela, C:
Inst Invest Biomed Bellvitge IDIBELL, Nephrol & Renal Transplantat Grp, Translat Med Area, Lhospitalet De Llobregat, Spain
Bertolino, E:
Inst Invest Biomed Bellvitge IDIBELL, Nephrol & Renal Transplantat Grp, Translat Med Area, Lhospitalet De Llobregat, Spain
Paloschi, V:
Tech Univ Munich, Dept Vasc & Endovasc Surg, Munich, Germany
Maegdefessel, L:
Tech Univ Munich, Dept Vasc & Endovasc Surg, Munich, Germany
Escolà-Gil, JC:
Inst Recerca St Pau Ctr CERCA, Barcelona, Spain
CIBER Diabet & Enfermedades Metab Asociadas, Barcelona, Spain
Aran, JM:
Inst Invest Biomed Bellvitge IDIBELL, Immune inflammatory Proc & Gene Therapeut Grp, Lhospitalet De Llobregat, Spain
Sbraga, F:
Hosp Univ Bellvitge, Dept Cardiac Surg, Lhospitalet De Llobregat, Spain
Blasco-Lucas, A:
Hosp Univ Bellvitge, Dept Cardiac Surg, Lhospitalet De Llobregat, Spain
Torras, J:
Hosp Univ Bellvitge, Dept Nephrol, Lhospitalet De Llobregat, Spain
Navarro, E:
Germans Trias & Pujol Res Inst IGTP, REMAR Grp, Badalona, Spain
Hueso, M:
Inst Invest Biomed Bellvitge IDIBELL, Nephrol & Renal Transplantat Grp, Translat Med Area, Lhospitalet De Llobregat, Spain
Hosp Univ Bellvitge, Dept Nephrol, Lhospitalet De Llobregat, Spain
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