Metformin-Loaded Alginate Nanoparticles Inhibits Mouse Atherosclerosis by Regulating Macrophage Differentiation by Activating the Adenosine Monophosphate-Activated Protein Kinase/Signal Transducer and Activator of Transcription 3 Pathway

Abstract

Objective: By modulating macrophage phenotype and the adenylate-activated protein kinase/signal transducer and activator of transcription 3 (STAT3) signaling pathway, metformin-loaded alginate nanoparticles may prevent atherosclerosis (As). Methods: Flow cytometry was used to determine the percentage of macrophages with distinct phenotypes (CD86 and CD206). Analysis of protein expression levels of iNOS, arginase 1, AMPK, pAMPK, STAT3 and phosphorylated STAT3 were performed by Western Blot. To confirm the in vitro findings, ApoE−/− mice were employed. Results: AMPK activity and the fraction of M2 macrophages dramatically increased in cells treated with Met, but STAT3 activity was considerably reduced. It was also shown that the Met group had much shorter aortas and lower levels of lipid deposition than that of the control group; also, the fraction of M1 macrophages in the lipid plaques of the animals treated with Met was dramatically reduced by using immunofluorescence labeling. There was a considerable increase in AMPK activity in the Met group, but STAT3 activity was dramatically lowered. Conclusion: According to the results of this study, STAT3 activity is regulated by activation of AMPK and macrophage development in plaques is prevented in mice by metformin-loaded alginate nanoparticles.