ArticleCirculation2024
Proteogenomic Data Integration Reveals CXCL10 as a Potentially Downstream Causal Mediator for IL-6 Signaling on Atherosclerosis.
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- A multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway.Cardiovascular research · 2025Pooled it
- Chemokine CXCL10 and Incident Stroke Risk in the Northern Manhattan Study.Translational stroke research · 2026Article
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- Lipoprotein metabolism and inflammation in healthy young subjects - exploring the postprandial and postabsorptive phases following intake of a standardized meal.Atherosclerosis plus · 2026Article
- Interleukin-6 as an Oral-Vascular Inflammatory Bridge: Integrating CXCL10 and Haptoglobin 2-2 into a Potential Model of Periodontitis-Associated Cardiovascular Risk.International journal of molecular sciences · 2026Review
- Identification of potential biological biomarkers for acute ischemic stroke based on integrated bioinformatics analyses.BMC neurology · 2026Article
- TheJournal of the American Heart Association · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Interleukin-6 Signaling Mediates Mitochondrial Fragmentation and Mitophagy Impairment to Induce Macrophages Ferroptosis in Atherosclerosis.Inflammation · 2026Article
- Genetic Variation in the Chemokine Network and Atherosclerosis Risk.Current atherosclerosis reports · 2026Review
- Genetic insights into radiomic and proteomic changes under β1-blockers treatment in hypertensive heart disease and hypertrophic cardiomyopathy.BMC medicine · 2026Article
- Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction.Current atherosclerosis reports · 2026Review
- Interleukin-6 blockade modulates monocyte recruitment to protect against diastolic dysfunction associated with inflammatory arthritis.Arthritis research & therapy · 2026Article
- Remote ischemic preconditioning in elderly patients with acute myocardial infarction and transient ischemic attack: a retrospective cohort study.Frontiers in cardiovascular medicine · 2026Article
- Clinical retrospective study on serum sCD163 and CXCL10 in the immune microenvironment of carotid atherosclerosis: association with inflammatory cytokines, immune cell subsets, and disease progression.Frontiers in immunology · 2026Article
- Three-Dimensional Perspectives on Inflammatory Regulation in Coronary Atherosclerosis: Integrated Mechanisms of Endothelial Priming, Lipid Metabolism, and Cytokine Synergy.Reviews in cardiovascular medicine · 2026Review
- Inflammatory drivers of carotid atherosclerosis: signaling pathways, immune cells, and plaque stability.Frontiers in cardiovascular medicine · 2026Review
- The role of IL-6 in atherosclerosis: a narrative review.Frontiers in cardiovascular medicine · 2026Review
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- Genetic insights into drug targets for alzheimer's disease: integrative multi-omics analysis.Alzheimer's research & therapy · 2025Article
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Authors and funding
20 authors at 11 institutions in 7 countries.
Funding
Abstract
backgroundGenetic and experimental studies support a causal involvement of IL-6 (interleukin-6) signaling in atheroprogression. Although trials targeting IL-6 signaling are underway, any benefits must be balanced against an impaired host immune response. Dissecting the mechanisms that mediate the effects of IL-6 signaling on atherosclerosis could offer insights about novel drug targets with more specific effects.
methodsLeveraging data from 522 681 individuals, we constructed a genetic instrument of 26 variants in the gene encoding the IL-6R (IL-6 receptor) that proxied for pharmacological IL-6R inhibition. Using Mendelian randomization, we assessed its effects on 3281 plasma proteins quantified with an aptamer-based assay in the INTERVAL cohort (n=3301). Using mediation Mendelian randomization, we explored proteomic mediators of the effects of genetically proxied IL-6 signaling on coronary artery disease, large artery atherosclerotic stroke, and peripheral artery disease. For significant mediators, we tested associations of their circulating levels with incident cardiovascular events in a population-based study (n=1704) and explored the histological, transcriptomic, and cellular phenotypes correlated with their expression levels in samples from human atherosclerotic lesions.
resultsWe found significant effects of genetically proxied IL-6 signaling on 70 circulating proteins involved in cytokine production/regulation and immune cell recruitment/differentiation, which correlated with the proteomic effects of pharmacological IL-6R inhibition in a clinical trial. Among the 70 significant proteins, genetically proxied circulating levels of CXCL10 (C-X-C motif chemokine ligand 10) were associated with risk of coronary artery disease, large artery atherosclerotic stroke, and peripheral artery disease, with up to 67% of the effects of genetically downregulated IL-6 signaling on these end points mediated by decreases in CXCL10. Higher midlife circulating CXCL10 levels were associated with a larger number of cardiovascular events over 20 years, whereas higher
conclusionsIntegrating multiomics data, we found a proteomic signature of IL-6 signaling activation and mediators of its effects on cardiovascular disease. Our analyses suggest the interferon-γ-inducible chemokine CXCL10 to be a potentially causal mediator for atherosclerosis in 3 vascular compartments and, as such, could serve as a promising drug target for atheroprotection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.