Geniposide alleviates atherosclerosis by regulating macrophage polarization via the FOS/MAPK signaling pathway - 14/03/20
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| Autres | 0 |
Graphical abstract |
Highlights |
• | Geniposide could attenuate atherosclerosis in high-fat diet fed New Zealand rabbits. |
• | Geniposide may inhibit inflammation and attenuate the extent of atherosclerotic lesions in high-fat diet fed rabbits. |
• | Geniposide may decrease the iNOS, IL-1β and elevate the Arg-1, IL-10 expression in high-fat diet rabbits. |
• | Geniposide may regulate macrophage polarization phenotype at least partially through the FOS/MAPK signaling pathway. |
Abstract |
Objective |
To assess geniposide’s effects in New Zealand rabbits with high-fat diet induced atherosclerosis and to explore the underpinning mechanisms.
Materials and methods |
Aorta histological changes were evaluated by intravenous ultrasound (IVUS) and H&E staining. Lipid accumulation in the aortic was quantified by Oil Red O staining. Then, RNA sequencing (RNA-seq) was carried out for detecting differentially expressed genes in rabbit high-fat diet induced atherosclerosis. The levels of the cytokines CRP, IL-1β and IL-10 were determined by ELISA. Protein levels of iNOS and Arg-1 were assessed by Western blot and immunohistochemical staining. The mRNA expression levels of NR4A1, CD14, FOS, IL1A, iNOS and Arg-1 were detected by quantitative real-time PCR (qPCR).
Results |
Geniposide markedly reduced the degree of atherosclerotic lesions in aorta tissues. RNA-seq and qPCR demonstrated that NR4A1, CD14, FOS and IL1A mRNA amounts were overtly increased in New Zealand rabbits with high-fat diet induced atherosclerosis. Moreover, geniposide reduced iNOS (M1 phenotype) mRNA and protein amounts as well as IL-1β secretion, which were enhanced in New Zealand rabbits with high-fat diet induced atherosclerosis. Besides, Arg-1 (M2 phenotype) mRNA and protein amounts were significantly increased after geniposide treatment, as well as IL-10 secretion.
Conclusion |
These findings suggest that geniposide could inhibit the progression of and stabilize atherosclerotic plaques in rabbits by suppressing M1 macrophage polarization and promoting M2 polarization through the FOS/MAPK signaling pathway.
Le texte complet de cet article est disponible en PDF.Keywords : Atherosclerosis, Macrophage polarization, Geniposide, New Zealand rabbit, MAPK signaling pathway
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Vol 125
Article 110015- mai 2020 Retour au numéro
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