ArticleBasic research in cardiology2016
Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression.
Article in Basic research in cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- NLRP3 mediates lipid-driven macrophage proliferation in established atherosclerosis.Basic research in cardiology · 2025Article
- Association of systemic inflammatory response index with ST segment elevation myocardial infarction and degree of coronary stenosis: a cross-sectional study.BMC cardiovascular disorders · 2024Article
- Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights.Frontiers in oncology · 2024Review
- Mitochondrial dysfunction and metabolic reprogramming induce macrophage pro-inflammatory phenotype switch and atherosclerosis progression in aging.Frontiers in immunology · 2024Article
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- Association of Systemic Inflammatory Response Index and Pan-Immune-Inflammation-Value with Long-Term Adverse Cardiovascular Events in ST-Segment Elevation Myocardial Infarction Patients After Primary Percutaneous Coronary Intervention.Journal of inflammation research · 2023Article
- Prognostic value of systemic inflammatory response index in patients with acute coronary syndrome undergoing percutaneous coronary intervention.Annals of medicine · 2022Article
- The interaction between nanoparticles and immune system: application in the treatment of inflammatory diseases.Journal of nanobiotechnology · 2022Review
- Macrophages in Atheromatous Plaque Developmental Stages.Frontiers in cardiovascular medicine · 2022Review
- Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in ApoeMolecular metabolism · 2021Article
- Pro-atherogenic actions of signal transducer and activator of transcription 1 serine 727 phosphorylation in LDL receptor deficient mice via modulation of plaque inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Recognition of Oxidized Lipids by Macrophages and Its Role in Atherosclerosis Development.Biomedicines · 2021Review
- Adjustment of the GRACE Risk Score by Monocyte to High-Density Lipoprotein Ratio Improves Prediction of Adverse Cardiovascular Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.Frontiers in cardiovascular medicine · 2021Article
- Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering.Basic research in cardiology · 2020Article
- Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice.Scientific reports · 2019Article
- Imaging mass spectrometry reveals heterogeneity of proliferation and metabolism in atherosclerosis.JCI insight · 2019Article
- Ablation of Myeloid ADK (Adenosine Kinase) Epigenetically Suppresses Atherosclerosis in ApoEArteriosclerosis, thrombosis, and vascular biology · 2018Article
- [Spleen tyrosine kinase inhibits proliferation and promotes apoptosis of colorectal cancer cells in vitro via regulating Fra-1].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Monocyte Recruitment Versus Macrophage Proliferation in Atherosclerosis.Circulation research · 2017Article
- Applying nanomedicine in maladaptive inflammation and angiogenesis.Advanced drug delivery reviews · 2017Review
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 4 countries.
Funding
Abstract
Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL-3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression.
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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.