Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox‑LDL‑induced THP‑1 monocytes
- Yihan Zhao
- Yizhen Zhao
- Yuan Tian
- Yang Zhou
Affiliations: Department of Cardiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China, Department of Neurosurgery, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Clinical Research Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550000, P.R. China, Department of Vascular Surgery, Deyang People's Hospital, Deyang, Sichuan 618000, P.R. China
- Published online on: August 24, 2022 https://doi.org/10.3892/etm.2022.11573
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Numerous studies have shown that the formation of foam cells is of vital importance in the process of atherosclerosis. The aim of the present study was to assess the effects of metformin on foam cell formation in oxidized low‑density lipoprotein (ox‑LDL)‑treated THP‑1 cells and explore its associated mechanism of action. Human monocytic THP‑1 cells were pretreated with metformin for 2 h and subsequently treated with ox‑LDL for 24 h. The data indicated that metformin significantly inhibited lipid accumulation in ox‑LDL‑treated THP‑1 cells by decreasing the expression of scavenger receptor A, cluster of differentiation 36 and adipocyte enhancer‑binding protein 1. In addition, metformin increased the expression levels of scavenger receptor B1 and ATP binding cassette transporter G1 and suppresses the esterification of free cholesterol. Furthermore, it markedly inhibited ferroptosis (reflected by the upregulation of glutathione peroxidase glutathione peroxidase 4 and the downregulation of Heme oxygenase‑1). In addition, it caused a marked suppression in the expression levels of cysteinyl aspartate specific proteinase‑1, IL‑1β, NOD‑like receptor protein 3, IL‑18 secretion and in the levels of oxidative stress. Metformin attenuated the activation of ERK and facilitated the phosphorylation of 5' adenosine monophosphate‑activated protein kinase (AMPK). Treatment of THP‑1 cells with an ERK inhibitor reversed these effects, while inhibition of AMPK activity exacerbated the effects noted in ox‑LDL‑treated THP‑1 cells. In conclusion, the present study suggested that metformin suppressed foam cell formation, inflammatory responses and inhibited ferroptosis in ox‑LDL‑treated macrophages via the AMPK/ERK signaling pathway.