ArticleThe American journal of pathology2009
Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 309 citations in OpenAlex.
- The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction.Journal of thrombosis and thrombolysis · 2014Trial
- Reduced Membrane CD163 Expression in 7-Oxysterol-Induced Apoptosis Accompanied by Elevated Oxidative Stress.Cells · 2026Article
- Loss of energy homeostasis contributes to hepatic damage development in sickle cell disease.Molecular metabolism · 2026Article
- Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?International journal of molecular sciences · 2025Review
- Increased CD163+ Macrophage Activation and High Expression of CD163 Promote Granulosa Cell Apoptosis in Polycystic Ovary Syndrome.Journal of inflammation research · 2025Article
- Molecular mechanisms and therapeutic progress in atherosclerosis: bridging immune inflammation and precision medicine.Frontiers in immunology · 2025Review
- Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics.Basic research in cardiology · 2024Review
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Macrophage profiling in atherosclerosis: understanding the unstable plaque.Basic research in cardiology · 2024Review
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Serum heme oxygenase-1 as a prognostic biomarker in patients with acute exacerbation of interstitial lung disease.Scientific reports · 2023Article
- Role of the pioneer transcription factor GATA2 in health and disease.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Macrophage immunometabolism in diabetes-associated atherosclerosis.Immunometabolism (Cobham, Surrey) · 2023Review
- M1/M2 macrophages and their overlaps - myth or reality?Clinical science (London, England : 1979) · 2023Article
- The Double-Edged Sword of Erythrocytes in Health and Disease via Their Adhesiveness.International journal of molecular sciences · 2023Review
- Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars.Experimental dermatology · 2023Review
- Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1.Antioxidants (Basel, Switzerland) · 2023Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Intraplaque hemorrhage accelerates atherosclerosis via oxidant stress and contributes to lesion development and destabilization. Normally, macrophages scavenge hemoglobin-haptoglobin (HbHp) complexes via CD163, and this process provokes the secretion of the anti-inflammatory atheroprotective cytokine interleukin (IL)-10. We therefore tested the hypothesis that HbHp complexes may drive monocyte differentiation to an atheroprotective phenotype. Examination of the macrophage phenotype in hemorrhaged atherosclerotic plaques revealed a novel hemorrhage-associated macrophage population (HA-mac), defined by high levels of CD163, but low levels of human leukocyte antigen-DR. HA-mac contained more iron, a pro-oxidant catalyst, but paradoxically had less oxidative injury, measured by 8-oxo-guanosine content. Differentiating monocytes with HbHp complexes reproduced the CD163(high) human leukocyte antigen-DR(low) HA-mac phenotype in vitro. These in vitro HA-mac cells cleared Hb more quickly, and consistently showed less hydrogen peroxide release, highly reactive oxygen species and oxidant stress, and increased survival. Differentiation to HA-mac was prevented by neutralizing IL-10 antibodies, indicating that IL-10 mediates an autocrine feedback mechanism in this system. Nonlinear dynamic modeling showed that an IL-10/CD163-positive feedback loop drove a discrete HA-mac lineage. Simulations further indicated an all-or-none switch to HA-mac at threshold levels of HbHp, and this conversion was experimentally verified. These data demonstrate the creation of a novel atheroprotective (HA-mac) macrophage subpopulation in response to intraplaque hemorrhage and raise the possibility that therapeutically reproducing this macrophage phenotype may be cardio-protective in cases of atherosclerosis.
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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.