动脉粥样硬化铁死亡相关基因的筛选和分析

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[中图分类号]R543.5 ［文献标志码］A [文章编号] 1671-7783（2025）04-0292-12

DOI： 10.13312/j.issn.1671-7783.y240225

[引用格式]，等.动脉粥样硬化铁死亡相关基因的筛选和分析[J].江苏大学学报（医学版）2025，35（4）：292-303.

Screening and analysis of ferroptosis-related genes in atherosclerosis

LI Yi⋅1 ， FAN Ye 1，2 ， ZHANG Ziyun 1 ， LIANG Lu 1 ，CONG Li1 （204 （1.HunanNomalUniversityHealthScienceCenter，ChangshaHunan41013；2.DepartmentofPathology，theSecondPeople'sHospital ofHunan Province，Changsha Hunan 41OO13，China）

[Abstract]Objective：To figure out the possible mechanisms of ferroptosis and explore potential ferroptosis-related genes （FRGs） biomarkers and pharmacological compounds for atherosclerosis（AS）.

Methods： The AS transcriptome dataset GSE100927 was downloaded from the gene expression omnibus（GEO）database.FRGs were downloaded from FerrDb database.To screen the ferroptosisrelated hub genes in AS （FRG-hubs） by weighted gene co-expression network analysis，diferential gene analysis，LASSO regression and random forest algorithm. Single-sample gene set enrichment （ssGSEA） analysis was used to evaluate the immunological landscape. Furthermore， transcription factors and miRNAs regulatory networks were constructed by the NetworkAnalyst database，and candidate drugs were searched from DSigDB database. The expression of FRG-hubs was verified by AS model mice. Results： zinc finger E-Box binding homeobox 1（ZEB1），mitogen-activated protein kinase kinase kinase 11（MAP3Kl1），and cyclin dependent kinase inhibitor 2A（CDKN2A） were identified as FRG-hubs， and the nomogram model based on them demonstrated high reliability and effctiveness.In addition， FRG-hubs and immune cellinfiltration showed a significant association. AS patients could be classified into2 ferroptosis-related cluster with diferent immune cell infiltration.Predictions were made for 13 transcription factors，8 miRNAs，and 10 drugs targeting FRG-hubs. The results of qRT-PCR and Western blotting show that compared with the control group，the mRNA and protein expression levels of Map3k11 and Cdkn2a are significantly elevated in the AS model mice，while the expresson level of the Zebl is significantly decreased. Conclusion： ZEB1，MAP3K11 and CDKN2A may be involved in the occurrence and development of AS by regulating immune-related pathways through ferroptosis.

[Key words]atherosclerosis； ferroptosis；immunity；survival prognosis

动脉粥样硬化（atherosclerosis，AS）是心血管疾病的主要表现，是一种由内皮细胞损伤引发的慢性炎症状态，以脂质积累和动脉壁内炎症级联反应为特征[1]。（剩余16769字）