ArticleBlood2016
Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE-/- mice and activate platelets via TLR2.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Product of arachidonic acid oxidation inhibits neutrophil migration by forming the inflammatory substrate for integrin αMβ2.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.Cellular and molecular gastroenterology and hepatology · 2024Review
- Mechanism of Tumor-Platelet Communications in Cancer.Circulation research · 2023Article
- Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow.Journal of immunology research · 2023Article
- Mechanism Research of Platelet Core Marker Prediction and Molecular Recognition in Cardiovascular Events.Combinatorial chemistry & high throughput screening · 2023Article
- Insight into the Evolving Role of PCSK9.Metabolites · 2022Review
- Pleiotropic Effects of PCSK9: Focus on Thrombosis and Haemostasis.Metabolites · 2022Review
- The OSE complotype and its clinical potential.Frontiers in immunology · 2022Review
- Inflammation-dependent oxidative stress metabolites as a hallmark of amyotrophic lateral sclerosis.Free radical biology & medicine · 2022Article
- Article
- Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword.International journal of molecular sciences · 2021Review
- Is Antiplatelet Therapy Contraindicated After Platelet-Rich Plasma Treatment? A Narrative Review.Orthopaedic journal of sports medicine · 2021Review
- Pleiotropic Effects of PCSK-9 Inhibitors.International journal of molecular sciences · 2021Review
- Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Non-Alloimmune Mechanisms of Thrombocytopenia and Refractoriness to Platelet Transfusion.Transfusion medicine reviews · 2020Review
- The Immune Nature of Platelets Revisited.Transfusion medicine reviews · 2020Review
- The Role of Toll-like Receptors in Atherothrombotic Cardiovascular Disease.ACS pharmacology & translational science · 2020Review
- Platelets as Mediators of Neuroinflammation and Thrombosis.Frontiers in immunology · 2020Review
- Inhibition of integrin αThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A prothrombotic state and increased platelet reactivity are common in dyslipidemia and oxidative stress. Lipid peroxidation, a major consequence of oxidative stress, generates highly reactive products, including hydroxy-ω-oxoalkenoic acids that modify autologous proteins generating biologically active derivatives. Phosphatidylethanolamine, the second most abundant eukaryotic phospholipid, can also be modified by hydroxy-ω-oxoalkenoic acids. However, the conditions leading to accumulation of such derivatives in circulation and their biological activities remain poorly understood. We now show that carboxyalkylpyrrole-phosphatidylethanolamine derivatives (CAP-PEs) are present in the plasma of hyperlipidemic ApoE(-/-) mice. CAP-PEs directly bind to TLR2 and induces platelet integrin αIIbβ3 activation and P-selectin expression in a Toll-like receptor 2 (TLR2)-dependent manner. Platelet activation by CAP-PEs includes assembly of TLR2/TLR1 receptor complex, induction of downstream signaling via MyD88/TIRAP, phosphorylation of IRAK4, and subsequent activation of tumor necrosis factor receptor-associated factor 6. This in turn activates the Src family kinases, spleen tyrosine kinase and PLCγ2, and platelet integrins. Murine intravital thrombosis studies demonstrated that CAP-PEs accelerate thrombosis in TLR2-dependent manner and that TLR2 contributes to accelerate thrombosis in mice in the settings of hyperlipidemia. Our study identified the novel end-products of lipid peroxidation, accumulating in circulation in hyperlipidemia and inducing platelet activation by promoting cross-talk between innate immunity and integrin activation signaling pathways.
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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.