Abstract:

Objective To investigate whether ferroptosis is present in atherosclerosis（AS）induced by high⁃fat diet and in the process of foam cell formation. Methods ApoE-/- mice fed with high⁃fat diet were used to establish an AS model；RAW264.7 macrophages pretreated with oxidized low density lipoprotein（ox ⁃LDL）were used to establish a foam cell model. Serum levels of triglyceride（TG），total cholesterol（TC），low⁃density lipoprotein cholesterol（LDL⁃C）and high density lipoprotein cholesterol（HDL⁃C）were detected by an automatic biochemistry analyzer. H&E and Oil Red O staining were used to observe plaque formation and lipid accumulation in mice aortic roots. mRNA and protein expressions of p53，GPX4 and SLC7A11 in aortic tissues and foam cells were detected by qRT ⁃ PCR and Western blot. Intracellular levels of malondialdehyde（MDA），glutathione（GSH）and Fe2 + were measured by MTS colorimetry；and level of reactive oxygen species（ROS）was detected by Fluorescent probe DCFH⁃DA. Results As compared with the control group，mRNA and protein expression of ferroptosis⁃related P53 was markedly increased，In RAW264.7 macrophage⁃derived foam cells induced by ox⁃LDL，mRNA and protein expressions of p53 increased significantly，whereas mRNA and protein expressions of GPX4 and SLC7A11 decreased significantly. Production of lipid peroxide ROS and MDA in cells increased，Fe2 + level increased，and GSH content significantly decreased. Conclusions Ferroptosis is involved in development of atherosclerosis induced by high⁃fat diet in ApoE-/- mice， and lipid peroxidation and ferroptosis in RAW264.7 macrophage ⁃ derived foam cells induced by ox ⁃ LDL are in⁃ creased，which may be related with the formation of atherosclerosis.

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