{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:17:21Z","timestamp":1793647041356,"version":"4.5.1"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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). <jats:italic>In vitro<\/jats:italic> experiments showed that dysregulated lipid metabolism promotes ferroptosis, and inhibition of ferroptosis improves mitochondrial and lysosomal dysfunction and suppresses endoplasmic reticulum stress. Ferrostatin-1, an ferroptosis inhibitor, attenuated the ox-LDL-induced upregulation of CYBB, HMOX1, IL1B, TYROBP, and CSF1R genes. A nomogram for predicting AS risk was constructed incorporating the expression levels of these five validated Hub genes. Single-cell data analysis results suggested that these genes were highly expressed in foam cells, inflammatory macrophages, smooth muscle cells, and helper T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In AS, abnormal lipid metabolism may drive ferroptosis via key regulatory genes (CYBB, HMOX1, IL1B, TYROBP, CSF1R), while also reshaping the immune microenvironment, potentially through the modulation of organelle function.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1642984","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:31Z","timestamp":1755144631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Abnormal lipid metabolism and atherosclerosis: a new perspective on organelle function regulation and ferroptosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xize","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qicheng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijia","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12970","article-title":"Atherosclerosis: Pathophysiology of insulin resistance, hyperglycemia, hyperlipidemia, and inflammation","volume":"12","author":"Beverly","year":"2020","journal-title":"J Diabetes"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2018.05.010","article-title":"Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis - Novel insights and future directions in diagnosis and therapy","volume":"29","author":"Hartley","year":"2019","journal-title":"Trends Cardiovasc Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.11909\/j.issn.1671-5411.2020.01.001","article-title":"China cardiovascular diseases report 2018: an updated summary","volume":"17","author":"Ma","year":"2020","journal-title":"J Geriatr Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/s41419-021-04054-3","article-title":"Ferroptosis: the potential value target in atherosclerosis","volume":"12","author":"Ouyang","year":"2021","journal-title":"Cell Death Dis"},{"key":"B6","article-title":"The lipid infiltration theory of atherosclerosis","volume":"30","author":"Dargel","year":"1989","journal-title":"Z Med Lab Diagn"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1038\/s41598-018-22292-y","article-title":"Identification of genomic differences among peripheral arterial beds in atherosclerotic and healthy arteries","volume":"8","author":"Steenman","year":"2018","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-013-9310-2","article-title":"Identification of two genes potentially associated in iron-heme homeostasis in human carotid plaque using microarray analysis","volume":"38","author":"Ayari","year":"2013","journal-title":"J Biosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.046755","article-title":"Auto-antigenic protein-DNA complexes stimulate plasmacytoid dendritic cells to promote atherosclerosis","volume":"125","author":"D\u00f6ring","year":"2012","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3848","article-title":"Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease","volume":"6","author":"Biros","year":"2015","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/s42003-022-04056-7","article-title":"Decoding the transcriptome of calcified atherosclerotic plaque at single-cell resolution","volume":"5","author":"Alsaigh","year":"2022","journal-title":"Commun Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac935","article-title":"FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations","volume":"51","author":"Zhou","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling tumor infiltrating immune cells with CIBERSORT","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/mps3040064","article-title":"Become Competent within One Day in Generating Boxplots and Violin Plots for a Novice without Prior R Experience","volume":"3","author":"Hu","year":"2020","journal-title":"Methods Protoc"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq170","article-title":"ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking","volume":"26","author":"Wilkerson","year":"2010","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinf"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-s4-s11","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","volume":"8","author":"Chin","year":"2014","journal-title":"BMC Syst Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12665","article-title":"Controlling the false discoveries in LASSO","volume":"73","author":"Huang","year":"2017","journal-title":"Biometrics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23010052","article-title":"Selecting feature subsets based on SVM-RFE and the overlapping ratio with applications in bioinformatics","volume":"23","author":"Lin","year":"2017","journal-title":"Molecules"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinf"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2689","article-title":"DGIdb: mining the druggable genome","volume":"10","author":"Griffith","year":"2013","journal-title":"Nat Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.733229","article-title":"The role of ferroptosis in cardiovascular disease and its therapeutic significance","volume":"8","author":"Chen","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e2100396","DOI":"10.1002\/adbi.202100396","article-title":"Lipid metabolism in ferroptosis","volume":"5","author":"Lin","year":"2021","journal-title":"Adv Biol (Weinh)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116289","article-title":"DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia","volume":"308","author":"Wu","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2217\/14796678.5.1.83","article-title":"Role of NADPH oxidase in atherosclerosis","volume":"5","author":"Violi","year":"2009","journal-title":"Future Cardiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/nu16162587","article-title":"The role of antioxidants in the therapy of cardiovascular diseases-A literature review","volume":"16","author":"M\u0142ynarska","year":"2024","journal-title":"Nutrients"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-024-01039-6","article-title":"Role of ROS and autophagy in the pathological process of atherosclerosis","volume":"80","author":"Zhu","year":"2024","journal-title":"J Physiol Biochem"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000012917.74432.66","article-title":"Superoxide production and expression of nox family proteins in human atherosclerosis","volume":"105","author":"Sorescu","year":"2002","journal-title":"Circulation"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.112.300438","article-title":"Reduced atherosclerotic burden in subjects with genetically determined low oxidative stress","volume":"33","author":"Violi","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102763","article-title":"NOX2 inhibition stabilizes vulnerable plaques by enhancing macrophage efferocytosis via MertK\/PI3K\/AKT pathway","volume":"64","author":"Wang","year":"2023","journal-title":"Redox Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.08.011","article-title":"Selective inactivation of NADPH oxidase 2 causes regression of vascularization and the size and stability of atherosclerotic plaques","volume":"242","author":"Quesada","year":"2015","journal-title":"Atherosclerosis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2016","article-title":"Heme oxygenases in cardiovascular health and disease","volume":"96","author":"Ayer","year":"2016","journal-title":"Physiol Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1379967","article-title":"The clinical relevance of heme detoxification by the macrophage heme oxygenase system","volume":"15","author":"Yeudall","year":"2024","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.devcel.2024.12.011","article-title":"HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis","volume":"60","author":"Peng","year":"2025","journal-title":"Dev Cell"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103345","article-title":"High expression levels of haem oxygenase-1 promote ferroptosis in macrophage-derived foam cells and exacerbate plaque instability","volume":"76","author":"Guo","year":"2024","journal-title":"Redox Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.88.5.506","article-title":"Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice","volume":"88","author":"Ishikawa","year":"2001","journal-title":"Circ Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.151720","article-title":"Heme oxygenase-1 expression in macrophages plays a beneficial role in atherosclerosis","volume":"100","author":"Orozco","year":"2007","journal-title":"Circ Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.16.8.1000","article-title":"Interleukin-1 beta in coronary arteries of patients with ischemic heart disease","volume":"16","author":"Galea","year":"1996","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.20.11.2394","article-title":"Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis","volume":"20","author":"Dewberry","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B45","first-page":"394","article-title":"Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion","volume":"121","author":"Bevilacqua","year":"1985","journal-title":"Am J Pathol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.08.011","article-title":"Inhibition of interleukin-1\u03b2 and reduction in atherothrombotic cardiovascular events in the CANTOS trial","volume":"76","author":"Everett","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s11883-020-00883-3","article-title":"Targeting inflammation to reduce residual cardiovascular risk","volume":"22","author":"Ajala","year":"2020","journal-title":"Curr Atheroscler Rep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.09.028","article-title":"Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond","volume":"70","author":"Libby","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1016\/j.molcel.2023.05.011","article-title":"IL-1\u03b2-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance","volume":"83","author":"Han","year":"2023","journal-title":"Mol Cell"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e20210518","DOI":"10.1084\/jem.20210518","article-title":"Ferroptosis in infection, inflammation, and immunity","volume":"218","author":"Chen","year":"2021","journal-title":"J Exp Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28518","article-title":"Iron-load exacerbates the severity of atherosclerosis via inducing inflammation and enhancing the glycolysis in macrophages","volume":"234","author":"Hu","year":"2019","journal-title":"J Cell Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1039241","article-title":"ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis","volume":"13","author":"Zheng","year":"2022","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2019.151058","article-title":"Mitochondria regulation in ferroptosis","volume":"99","author":"Wang","year":"2020","journal-title":"Eur J Cell Biol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2019.100840","article-title":"Mitochondrial bioenergetics and redox dysfunctions in hypercholesterolemia and atherosclerosis","volume":"71","author":"Oliveira","year":"2020","journal-title":"Mol Aspects Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.117.031589","article-title":"Dicer in macrophages prevents atherosclerosis by promoting mitochondrial oxidative metabolism","volume":"138","author":"Wei","year":"2018","journal-title":"Circulation"},{"key":"B56","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.freeradbiomed.2020.07.026","article-title":"Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell","volume":"160","author":"Bai","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"15515","DOI":"10.1038\/s41598-023-42760-4","article-title":"Oxidative stress induces mitochondrial iron overload and ferroptotic cell death","volume":"13","author":"Chen","year":"2023","journal-title":"Sci Rep"},{"key":"B59","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.molcel.2018.10.042","article-title":"Role of mitochondria in ferroptosis","volume":"73","author":"Gao","year":"2019","journal-title":"Mol Cell"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.07.006","article-title":"Emerging roles for the lysosome in lipid metabolism","volume":"27","author":"Thelen","year":"2017","journal-title":"Trends Cell Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e21635","DOI":"10.7554\/eLife.21635","article-title":"Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export","volume":"5","author":"Li","year":"2016","journal-title":"Elife"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695917","article-title":"STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites","volume":"36","author":"Wilhelm","year":"2017","journal-title":"EMBO J"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M002345","article-title":"MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein","volume":"51","author":"Charman","year":"2010","journal-title":"J Lipid Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.07.078","article-title":"Ferroptosis is a lysosomal cell death process","volume":"503","author":"Gao","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00859-z","article-title":"Organelle-specific regulation of ferroptosis","volume":"28","author":"Chen","year":"2021","journal-title":"Cell Death Differ"},{"key":"B66","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.semcancer.2019.03.002","article-title":"Ferroptosis is a type of autophagy-dependent cell death","volume":"66","author":"Zhou","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1016\/j.chembiol.2022.10.006","article-title":"Ferroptosis inhibition by lysosome-dependent catabolism of extracellular protein","volume":"29","author":"Armenta","year":"2022","journal-title":"Cell Chem Biol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e202302116","DOI":"10.26508\/lsa.202302116","article-title":"Improving lysosomal ferroptosis with NMN administration protects against heart failure","volume":"6","author":"Yagi","year":"2023","journal-title":"Life Sci Alliance"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00320-3","article-title":"Pharmacological targeting of endoplasmic reticulum stress in disease","volume":"21","author":"Marciniak","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.02.018","article-title":"Unraveling the role of ER stress inhibitors in the context of metabolic diseases","volume":"119","author":"Sarvani","year":"2017","journal-title":"Pharmacol Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S428482","article-title":"The role of adipocyte endoplasmic reticulum stress in obese adipose tissue dysfunction: A review","volume":"16","author":"Xu","year":"2023","journal-title":"Int J Gen Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2018.0438","article-title":"The interface between ER and mitochondria: molecular compositions and functions","volume":"41","author":"Lee","year":"2018","journal-title":"Mol Cells"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.224766","article-title":"The role of endoplasmic reticulum stress in the progression of atherosclerosis","volume":"107","author":"Tabas","year":"2010","journal-title":"Circ Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.338673","article-title":"Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation","volume":"287","author":"Oh","year":"2012","journal-title":"J Biol Chem"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10081167","article-title":"Roles and therapeutic implications of endoplasmic reticulum stress and oxidative stress in cardiovascular diseases","volume":"10","author":"Zhou","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1212215","article-title":"ER stress: an emerging regulator in GVHD development","volume":"14","author":"Choi","year":"2023","journal-title":"Front Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2022.0824","article-title":"X-box binding protein 1: an adaptor in the pathogenesis of atherosclerosis","volume":"14","author":"Wang","year":"2023","journal-title":"Aging Dis"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114897","article-title":"Endoplasmic reticulum stress-triggered ferroptosis via the XBP1-Hrd1-Nrf2 pathway induces EMT progression in diabetic nephropathy","volume":"164","author":"Liu","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.85883","article-title":"Melatonin ameliorates hepatic ferroptosis in NAFLD by inhibiting ER stress via the MT2\/cAMP\/PKA\/IRE1 signaling pathway","volume":"19","author":"Guan","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-08-0724","article-title":"Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells","volume":"22","author":"Matsushita","year":"2011","journal-title":"Mol Biol Cell"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.927641","article-title":"Inhibition of the IRE1\/JNK pathway in renal tubular epithelial cells attenuates ferroptosis in acute kidney injury","volume":"13","author":"Liang","year":"2022","journal-title":"Front Pharmacol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030695","article-title":"ER stress responses: an emerging modulator for innate immunity","volume":"9","author":"Di Conza","year":"2020","journal-title":"Cells"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.Mcr-18-0055","article-title":"Ferroptosis-induced endoplasmic reticulum stress: cross-talk between ferroptosis and apoptosis","volume":"16","author":"Lee","year":"2018","journal-title":"Mol Cancer Res"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.114123","article-title":"Cadmium induces liver dysfunction and ferroptosis through the endoplasmic stress-ferritinophagy axis","volume":"245","author":"He","year":"2022","journal-title":"Ecotoxicol Environ Saf"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.09.008","article-title":"Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells","volume":"175","author":"Zhao","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24308","article-title":"ATF6\u03b1 promotes prostate cancer progression by enhancing PLA2G4A-mediated arachidonic acid metabolism and protecting tumor cells against ferroptosis","volume":"82","author":"Zhao","year":"2022","journal-title":"Prostate"},{"key":"B87","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s42003-018-0212-6","article-title":"Golgi stress mediates redox imbalance and ferroptosis in human cells","volume":"1","author":"Alborzinia","year":"2018","journal-title":"Commun Biol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"4995","DOI":"10.26355\/eurrev_201808_15640","article-title":"Pravastatin improves atherosclerosis in mice with hyperlipidemia by inhibiting TREM-1\/DAP12","volume":"22","author":"Wang","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B89","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12944-020-01222-w","article-title":"Bioinformatics analysis of vascular RNA-seq data revealed hub genes and pathways in a novel Tibetan minipig atherosclerosis model induced by a high fat\/cholesterol diet","volume":"19","author":"Pan","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2023.2203185","article-title":"Identification and verification of pivotal genes promoting the progression of atherosclerosis based on WGCNA","volume":"51","author":"Wen","year":"2023","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.602908","article-title":"Identifying RBM47, HCK, CD53, TYROBP, and HAVCR2 as hub genes in advanced atherosclerotic plaques by network-based analysis and validation","volume":"11","author":"Liu","year":"2020","journal-title":"Front Genet"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.5551\/jat.52993","article-title":"IGFBP6 is downregulated in unstable carotid atherosclerotic plaques according to an integrated bioinformatics analysis and experimental verification","volume":"27","author":"Liu","year":"2020","journal-title":"J Atheroscler Thromb"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114247","article-title":"TREM2 protects against LPS-induced murine acute lung injury through suppressing macrophage ferroptosis","volume":"150","author":"Li","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0808497","article-title":"Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages","volume":"85","author":"Irvine","year":"2009","journal-title":"J Leukoc Biol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1161\/atvbaha.114.304723","article-title":"Regulation of Csf1r and Bcl6 in macrophages mediates the stage-specific effects of microRNA-155 on atherosclerosis","volume":"35","author":"Wei","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e16122","DOI":"10.7717\/peerj.16122","article-title":"Identification and validation of hub genes involved in foam cell formation and atherosclerosis development via bioinformatics","volume":"11","author":"Teng","year":"2023","journal-title":"PeerJ"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-023-00281-3","article-title":"Blockade of IL-6 signaling alleviates atherosclerosis in Tet2-deficient clonal hematopoiesis","volume":"2","author":"Liu","year":"2023","journal-title":"Nat Cardiovasc Res"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.111.239608","article-title":"G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors","volume":"32","author":"Wu","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.2147\/jir.S488288","article-title":"Unveiling the molecular links between atrial fibrillation and atherosclerosis: insights into shared pathogenesis and ferroptosis diagnostic biomarkers","volume":"17","author":"Xu","year":"2024","journal-title":"J Inflammation Res"},{"key":"B100","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2174\/1871525717666190114145137","article-title":"The cardiovascular protective effects of chrysin: A narrative review on experimental researches","volume":"17","author":"Farkhondeh","year":"2019","journal-title":"Cardiovasc Hematol Agents Med Chem"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e41272","article-title":"The therapeutic potential of apigenin against atherosclerosis","volume":"11","author":"Jiang","year":"2025","journal-title":"Heliyon"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13226792","article-title":"The co-existence of hypovitaminosis D and diabetes mellitus triples the incidence of severe coronary artery disease in women","volume":"13","author":"Aleksova","year":"2024","journal-title":"J Clin Med"},{"key":"B103","doi-asserted-by":"publisher","first-page":"e240056","DOI":"10.1530\/joe-24-0056","article-title":"Vitamin D reduces VSMC foam cell formation and protects against AS progression","volume":"265","author":"Zhang","year":"2025","journal-title":"J Endocrinol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s12012-025-09998-y","article-title":"Essential and non-essential metals and metalloids and their role in atherosclerosis","volume":"25","author":"Massie","year":"2025","journal-title":"Cardiovasc Toxicol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-019-09551-8","article-title":"Protective effect of RIVA against sunitinib-induced cardiotoxicity by inhibiting oxidative stress-mediated inflammation: probable role of TGF-\u03b2 and smad signaling","volume":"20","author":"Imam","year":"2020","journal-title":"Cardiovasc Toxicol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9500-9","article-title":"VEGF pathway inhibition by anticancer agent sunitinib and susceptibility to atherosclerosis plaque disruption","volume":"29","author":"Ropert","year":"2011","journal-title":"Invest New Drugs"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176437","article-title":"Drug repurposing screen identifies novel anti-inflammatory activity of sunitinib in macrophages","volume":"969","author":"Chaffey","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.124.319980","article-title":"Novel therapeutics and upcoming clinical trials targeting inflammation in cardiovascular diseases","volume":"44","author":"Potere","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-024-01241-3","article-title":"Targeting inflammatory pathways in atherosclerosis: exploring new opportunities for treatment","volume":"26","author":"d'Aiello","year":"2024","journal-title":"Curr Atheroscler Rep"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106157","article-title":"Targeting the residual cardiovascular risk by specific anti-inflammatory interventions as a therapeutic strategy in atherosclerosis","volume":"178","author":"Hafiane","year":"2022","journal-title":"Pharmacol Res"},{"key":"B111","doi-asserted-by":"publisher","first-page":"e0173981","DOI":"10.1371\/journal.pone.0173981","article-title":"Diacerein inhibits the pro-atherogenic & pro-inflammatory effects of IL-1 on human keratinocytes & endothelial cells","volume":"12","author":"Mohan","year":"2017","journal-title":"PloS One"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1998.tb01455.x","article-title":"Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro","volume":"83","author":"Ylitalo","year":"1998","journal-title":"Pharmacol Toxicol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"e38404","DOI":"10.1097\/md.0000000000038404","article-title":"Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis","volume":"103","author":"Xu","year":"2024","journal-title":"Med (Baltimore)"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11020343","article-title":"Antioxidant activity of natural hydroquinones","volume":"11","author":"Giner","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00819","article-title":"Nrf2 activation provides atheroprotection in diabetic mice through concerted upregulation of antioxidant, anti-inflammatory, and autophagy mechanisms","volume":"9","author":"Lazaro","year":"2018","journal-title":"Front Pharmacol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.bioorg.2013.11.001","article-title":"Syntheses of diacyltanshinol derivatives and their suppressive effects on macrophage foam cell formation by reducing oxidized LDL uptake","volume":"52","author":"Cheng","year":"2014","journal-title":"Bioorg Chem"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6584059","article-title":"A novel STAT3-mediated GATA6 pathway contributes to tert-butylhydroquinone- (tBHQ-) protected TNF\u03b1-activated vascular cell adhesion molecule 1 (VCAM-1) in vascular endothelium","volume":"2020","author":"Zhou","year":"2020","journal-title":"Oxid Med Cell Longev"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1642984\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:33Z","timestamp":1755144633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1642984\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":117,"alternative-id":["10.3389\/fimmu.2025.1642984"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1642984","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"article-number":"1642984"}}