ArticleCirculation. Cardiovascular genetics2014
Toll-like receptor 4 regulates platelet function and contributes to coagulation abnormality and organ injury in hemorrhagic shock and resuscitation.
Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03682757 (Post-Injury Platelet Biology), which is not on this map. Cited by 35 papers.
What it found
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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.
Post-Injury Platelet Biology: Mechanisms and Outcomes
Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- From Inflammation to Thrombosis: The Prothrombotic State and Cardiovascular Risk in Inflammatory Bowel Disease.Medicina (Kaunas, Lithuania) · 2026Review
- An integrative clinical and bioinformatic analysis identifies MicroRNAs as biomarkers of ischemic stroke severity.Scientific reports · 2026Article
- High platelet-to-red blood cell ratio and outcomes in trauma patients requiring massive transfusions.World journal of emergency surgery : WJES · 2025Observational
- From theory to platelets: unraveling the history and complexities of biased signaling.Blood vessels, thrombosis & hemostasis · 2025Review
- Plasma Fatty Acid Profiling and Mathematical Estimation of the Omega-3 Index: Toward Diagnostic Tools in Atherosclerosis and Statin Therapy Monitoring.Biomedicines · 2025Article
- A new perspective on cardiovascular function and dysfunction during endurance exercise: identifying the primary cause of cardiovascular risk.Biology of sport · 2024Article
- One immune cell to bind them all: platelet contribution to neurodegenerative disease.Molecular neurodegeneration · 2024Review
- Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9).Mediators of inflammation · 2024Review
- Severe Trauma-Induced Coagulopathy: Molecular Mechanisms Underlying Critical Illness.International journal of molecular sciences · 2023Review
- Retinal Proteome Analysis Reveals a Region-Specific Change in the Rabbit Myopia Model.International journal of molecular sciences · 2023Article
- Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow.Journal of immunology research · 2023Article
- Article
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- Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19.Seminars in cancer biology · 2022Review
- Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Inferring Tissue-Specific, TLR4-Dependent Type 17 Immune Interactions in Experimental Trauma/Hemorrhagic Shock and Resuscitation Using Computational Modeling.Frontiers in immunology · 2022Article
- Associations Among Disseminated Intravascular Coagulation, Thrombocytopenia Cytokines/Chemokines and Genetic Polymorphisms of Toll-Like Receptor 2/4 in Chinese Patients with Sepsis.Journal of inflammation research · 2022Article
- Trauma-induced coagulopathy.Nature reviews. Disease primers · 2021Review
- Review
- Dynamic effects of calcium on in vivo and ex vivo platelet behavior after trauma.The journal of trauma and acute care surgery · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGrowing evidence indicates that the presence of toll-like receptor 4 (TLR4) on platelets is a key regulator of platelet number and function. Platelets exposed to TLR4 agonists may serve to activate other cells such as neutrophils and endothelial cells in sepsis and other inflammatory conditions. The functional significance of platelet TLR4 in hemorrhagic shock (HS), however, remains unexplored. METHODS AND
resultsUsing thromboelastography and platelet aggregometry, we demonstrate that platelet function is impaired in a mouse model of HS with resuscitation. Further analysis using cellular-specific TLR4 deletion in mice revealed that platelet TLR4 is essential for platelet activation and function in HS with resuscitation and that platelet TLR4 regulates the development of coagulopathy after hemorrhage and resuscitation. Transfusion of TLR4-negative platelets into mice resulted in protection from coagulopathy and restored platelet function. Additionally, platelet-specific TLR4 knockout mice were protected from lung and liver injury and exhibited a marked reduction in systemic inflammation as measured by circulating interleukin-6 after HS with resuscitation.
conclusionsWe demonstrate for the first time that platelet TLR4 is an essential mediator of the inflammatory response as well as platelet activation and function in HS and resuscitation.
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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.