ArticleThe Journal of clinical investigation2017
Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 222 citations in OpenAlex.
- Effect of Admission Diabetes History on Safety and Efficacy of Early Tirofiban Infusion after Intravenous Thrombolysis in Ischaemic Stroke: a post-hoc analysis of the ASSET-IT trial.European stroke journal · 2026Trial
- S100A8/A9 and S100A12 Proteins and Macrophage Polarization: Therapeutic Targets in Atherosclerosis.Biomolecules · 2026Review
- Platelet hyperactivation drives oxidized mitochondrial DNA-induced neutrophil extracellular traps formation in biliary atresia.JHEP reports : innovation in hepatology · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Modulatory Effects of Polyphenols on Altered Leukocyte Functions in Thromboinflammation and Diabetes Mellitus.International journal of molecular sciences · 2026Review
- An overview of the role of platelets in vascular disease associated with diabetes mellitus.Hormones (Athens, Greece) · 2026Review
- Circulating S100A8/A9 drives faster platelet COX-1 recovery via MRP4, impairing the duration of aspirin response.Blood advances · 2026Article
- Calprotectin Is a Circulating Biomarker and Potential Therapeutic Target for Sarcopenia in Chronic Obstructive Pulmonary Disease.Journal of cachexia, sarcopenia and muscle · 2026Article
- Review
- Effect of acupuncture on brain microenvironment in rats with post-stroke limb spasticity based on single-cell transcriptome sequencing technology.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Clinical Utility of an Increased Pretreatment Immature Platelet Fraction in the Early Diagnosis of TAFRO Syndrome, Especially in Patients with Late-onset Thrombocytopenia: A Case Series and Literature Review.Internal medicine (Tokyo, Japan) · 2025Review
- Adipocyte death promotes hepatic infiltration of S100A8+ macrophages and steatotic liver disease progression in mice.The Journal of clinical investigation · 2025Article
- Immuno-haemostatic dysregulation in heart failure with preserved ejection fraction.ESC heart failure · 2025Article
- Characterizing the effect of bariatric surgery on circulating S100A9.International journal of obesity (2005) · 2025Article
- Kupffer cells are essential for platelet-mediated thrombopoietin generation in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Neutrophil Mobilization Triggers Microglial Functional Change to Exacerbate Cerebral Ischemia-Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SEC61B regulates calcium flux and platelet hyperreactivity in diabetes.The Journal of clinical investigation · 2025Article
- Neutrophil-Endothelium Interaction Mediated by S100A9 Promotes Pulmonary Vascular Remodeling During Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities.ESC heart failure · 2025Review
- Elevated levels of S100A8 and S100A9 exacerbate muscle mitochondrial fragmentation in sepsis-induced muscle atrophy.Communications biology · 2025Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis. IL-6 acts on hepatocytes to enhance the production of thrombopoietin, which in turn interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow progenitor cells to promote their expansion and proliferation, resulting in reticulated thrombocytosis. Lowering blood glucose using a sodium-glucose cotransporter 2 inhibitor (dapagliflozin), depleting neutrophils or Kupffer cells, or inhibiting S100A8/A9 binding to RAGE (using paquinimod), all reduced diabetes-induced thrombocytosis. Inhibiting S100A8/A9 also decreased atherogenesis in diabetic mice. Finally, we found that patients with type 2 diabetes have reticulated thrombocytosis that correlates with glycated hemoglobin as well as increased plasma S100A8/A9 levels. These studies provide insights into the mechanisms that regulate platelet production and may aid in the development of strategies to improve on current antiplatelet therapies and to reduce cardiovascular disease risk in diabetes.
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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.