ArticleThe Journal of clinical investigation2018
CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04367792 (Pathology and Pathogenesis of Cardiac Injury in COVID-19 Infections in Humans), which is not on this map. Cited by 204 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pathology and Pathogenesis of Cardiac Injury in COVID-19 Infections in Humans
Who cites it
204 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.Circulation. Cardiovascular imaging · 2022Trial
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- Single-cell transcriptomics provides insights into the stress-immune interplay and informs disease risk.Cell genomics · 2026Article
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- RNF213 in Panvascular Disease: A Molecular Hub Linking Genetic Susceptibility to Systemic Vasculopathy.Biomedicines · 2026Review
- EBV Triggers a Distinct Antiviral Response in HMC3 Cells.bioRxiv : the preprint server for biology · 2026Article
- Artery tertiary lymphoid organs, neuro-immune interaction and their mediators in atherosclerosis.Basic research in cardiology · 2026Review
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- 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
- Genetically predicted triglyceride levels and endometriosis risk: Mendelian randomization with exploratory multi-omics analyses.PloS one · 2026Article
- Preliminary Observations of Spatial Imbalance between Lymphangiogenesis and Angiogenesis within Carotid Atherosclerotic Plaques: A Pilot Histopathological Study.Annals of vascular diseases · 2026Article
- Shenzhu Guanxin formula alleviates atherosclerosis in rats via PI3K/Akt pathway inhibition: a comparative study of decoction and granule forms.American journal of translational research · 2026Article
- Cross-tissue single-cell atlas reveals Id2 promotes sepsis-induced tissue damage by mediating macrophage metabolic reprogramming via Pkm2.International journal of biological sciences · 2026Article
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- Gold Nanoparticles in Atherosclerosis: A Dual Approach to Diagnosis and Therapy.Molecular imaging and biology · 2025Review
- High-Throughput Tear Proteomics Reveals Multi-Faceted Signatures of Thyroid Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Identification of IL18/IL18R1 signaling as a predictive biomarker of SGLT2 inhibitor efficacy in type 2 diabetes.iScience · 2025Article
- Mitochondrial uptake and translocation by macrophages promotes vascular regeneration in peripheral ischemia.Bioactive materials · 2025Article
144 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 11 institutions in 3 countries.
Funding
Abstract
Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway.
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Registered trials
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.