Abnormal lipid metabolism and atherosclerosis: a new perspective on organelle function regulation and ferroptosis

作者：Xize Wu, Yuxi Huang, Jiaqi Ren, Xue Pan, Qingyu Wu, Qicheng Cai, Ruiying Wang, Teng Feng, Shan Gao, Bo Wang, Meijia Cheng, Yue Li, Lihong Gong · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1642984 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Single-cell and spatial transcriptomics、Immune cells in cancer

Background Atherosclerosis (AS), characterized by lipid accumulation, contributes significantly to global cardiovascular morbidity. Ferroptosis, an iron-dependent form of cell death triggered by lipid peroxidation, is emerging as a critical player in AS progression. Therefore, our study seeks to elucidate the intricate mechanisms of ferroptosis within the lipid metabolism pathway in AS. Methods Differentially expressed genes were identified from the GSE100927 dataset, subsequently isolating AS lipid metabolism-related ferroptosis genes (ASLMRFeGs). Unsupervised cluster analysis was performed on AS samples to identify molecular clusters. WGCNA was performed to uncover module Hub genes. Multiple machine learning models (LASSO, SVM-RFE, RF) were applied to screen Hub genes. Experimental validation was performed by ox-LDL-induced HUVECs and RAW 264.7 cells. Single-cell data analyzes the gene structure and gene expression status of individual cells. Results Six ASLMRFeGs (CTSB, CYBB, DPP4, HILPDA, HMOX1, IL1B) alter the immune microenvironment in AS. AS samples were stratified into two molecular clusters, exhibiting significant variations in inflammation and immune responses. Enrichment analysis of the 225 module Hub genes showed close association with inflammation, immune responses, cytoskeleton organization, and various organelles. Machine learning identified four candidate Hub genes (TYROBP, CSF1R, LCP2, C1QA). In vitro experiments showed that dysregulated lipid metabolism prom...