ArticleCirculation2022
AtheroSpectrum Reveals Novel Macrophage Foam Cell Gene Signatures Associated With Atherosclerotic Cardiovascular Disease Risk.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- PD-L1 rs2890658 Polymorphism Increases Risk for Non-Small-Cell Lung Cancer in Northern China Population Based on Experimental Data and Meta-Analysis.Contrast media & molecular imaging · 2022Pooled it
- Endothelial cells modulate immune cell responses during atherosclerosis.Trends in immunology · 2026Review
- A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques.Bioactive materials · 2026Article
- Increased atherosclerosis and expression of inflammarafts in macrophage foam cells in AIBP-deficient mice.Scientific reports · 2026Article
- Phytomedicines modulate pyroptosis in cardiovascular diseases: pre-clinical evidence, limitations and translational perspectives.Frontiers in pharmacology · 2026Review
- A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.Frontiers in immunology · 2026Review
- MGST3 defines a mitochondrial-health-associated M2 macrophage state in atherosclerosis: integrative multi-omics, single-cell mediation, and functional validation.Frontiers in immunology · 2026Article
- Mapping Macrophage Diversity in Coats' Disease: A Lipid-Associated Subset in the Pathogenesis of Exudative Retinopathy.Investigative ophthalmology & visual science · 2025Article
- Trans-omics landscape of systemic vasculitis identified matrix metalloproteinase 12 as a novel signature molecule.Rheumatology (Oxford, England) · 2025Article
- Genetic and pharmacological targeting of Snail inhibits atherosclerosis by relieving intraplaque endothelium dysfunction and associated inflammation.Acta pharmacologica Sinica · 2025Article
- Involvement of miRNA-204 carried by the exosomes of macrophages in the AT2 receptor-mediated improvement of vascular calcification.Cellular and molecular life sciences : CMLS · 2025Article
- Foamy macrophages in atherosclerosis: unraveling the balance between pro- and anti-inflammatory roles in disease progression.Frontiers in cardiovascular medicine · 2025Review
- Lipidomics-Based Identification of Plasma Lipid Biomarkers in Tuberculosis-Coronary Artery Disease Comorbidity.Infection and drug resistance · 2025Article
- Integrated Single-Cell Analysis Revealed Novel Subpopulations of Foamy Macrophages in Human Atherosclerotic Plaques.Biomolecules · 2024Article
- Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.Molecules (Basel, Switzerland) · 2024Review
- Lipid-associated macrophages reshape BAT cell identity in obesity.Cell reports · 2024Article
- The Multifaceted Nature of Macrophages in Cardiovascular Disease.Biomedicines · 2024Review
- Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.Lipids in health and disease · 2024Article
- Adopting artificial intelligence in cardiovascular medicine: a scoping review.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- LncRNA HOTAIR Inhibits miR-19a-3p to Alleviate Foam Cell Formation and Inflammatory Response in Atherosclerosis.International journal of medical sciences · 2024Article
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Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundWhereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to cardiovascular event risk. Monocytes and macrophages play central roles in atherosclerosis, but studies have yet to provide a detailed view of macrophage populations involved in increased ASCVD risk.
methodsA novel macrophage foaming analytics tool, AtheroSpectrum, was developed using 2 quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. A machine learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of MESA participants (Multi-Ethnic Study of Atherosclerosis; set 1; n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (30-gene cardiovascular disease risk score [CR-30]), which was subsequently validated in the remaining MESA participants (set 2; n=228); performance of CR-30 was also tested in 2 independent human atherosclerotic tissue transcriptome data sets (GTEx [Genotype-Tissue Expression] and GSE43292).
resultsUsing single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, and FR-FCM-Z23S), AtheroSpectrum detected 2 distinct programs in plaque macrophages-homeostatic foaming and inflammatory pathogenic foaming-the latter of which was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with cardiovascular event in MESA set 1. A cardiovascular disease risk score model (CR-30) was then developed by incorporating this gene set with traditional variables sensitive to cardiovascular event in MESA set 1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA set 2 (
conclusionsOur novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk.
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