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Volume 28, Issue 3
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

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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2024-01-10
2025-04-02

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/content/journals/cchts/10.2174/0113862073271348231213071225
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The Potential Association of TFR1/SLC11A2/GPX4 with Ferroptosis in Mediating Lipid Metabolism Disorders in Atherosclerosis
Comb Chem High Throughput Screen 28, 467 (2025); https://doi.org/10.2174/0113862073271348231213071225
/content/journals/cchts/10.2174/0113862073271348231213071225
/content/journals/cchts/10.2174/0113862073271348231213071225
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  • Article Type:     Research Article
Keyword(s): ApoE-/- mice; Atherosclerosis; fat metabolism; ferroptosis; GPX4; SLC11A2

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