脂质代谢
氧化应激
载脂蛋白E
GPX4
生物
炎症
转录组
脂代谢紊乱
细胞生物学
免疫学
内科学
医学
内分泌学
生物化学
超氧化物歧化酶
血脂
基因表达
胆固醇
疾病
基因
谷胱甘肽过氧化物酶
作者
Yuan Cao,Nan Song,Ying Wang,Xue Leng,Li Wang,Yixin Ma,Si Chen,Xing Ju,Lianqun Jia
出处
期刊:Combinatorial Chemistry & High Throughput Screening
[Bentham Science]
日期:2024-01-10
卷期号:27
被引量:2
标识
DOI:10.2174/0113862073271348231213071225
摘要
Purpose: Atherosclerosis is the most common and significant form of arterial disease, characterized primarily by lipid accumulation and inflammatory cell infiltration as its main pathological basis. This study aims to investigate the molecular mechanisms and associated pathways by which iron accumulation may be involved in lipid metabolism abnormalities in atherosclerotic mice. Methods: Relying on ApoE-/- mouse body position observation, blood biochemical analysis, oxidative stress test and aortic tissue sectioning techniques, the effects of ferroptosis on lipid metabolism in atherosclerotic mice were analyzed. Use RT-PCR analysis and transcriptomics tests to understand the specific molecular mechanism. Results: Our analysis reveals a correlation between Ferroptosis and elevated levels of TC, TG, ALT, AST, IL-1β, and TNF-α in the blood of atherosclerotic model mice. At the same time, it exacerbates the pathological changes of mouse aorta tissue. Our results suggest a potential link between ferroptosis and the dysregulation of TFR1/SLC11A2/GPX4 expression, along with the presence of oxidative stress, in the progression of AS. Transcriptomics results indicate that ferroptosis- mediated deterioration of atherosclerosis in ApoE-/- mice is potentially associated with cell phagocytosis, apoptosis involving TNF-α, and the expression of atherosclerotic and other process-related genes. Conclusion: Ferroptosis exacerbated the lipid metabolism disorder in atherosclerotic mice. The core mechanism of its effect is that ferroptosis activates the TFR1/SLC11A2/GPX4 signaling pathway, which leads to the up-regulation of oxidative stress in ApoE-/- mice, and ultimately aggravates the abnormal lipid metabolism in ApoE-/- mice.
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