ArticleBlood advances2021
A thrombin-PAR1/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C).
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Tissue factor in COVID-19-associated coagulopathy.Thrombosis research · 2022Pooled it
- Air Pollution Exposure Induces Vascular Endothelial Cell Dysfunction via Elevated Circulating F2: Multiomics Insights from anEnvironment & health (Washington, D.C.) · 2026Article
- Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry.Nature cardiovascular research · 2025Article
- Challenging the notion of endothelial infection by SARS-CoV-2: insights from the current scientific evidence.Frontiers in immunology · 2025Article
- Extracellular RNA Induces Neutrophil Recruitment Via Toll-Like Receptor 3 During Venous Thrombosis After Vascular Injury.Journal of the American Heart Association · 2024Article
- Article
- The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis.Current molecular medicine · 2024Review
- Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Hemostasis in arenavirus infection.Blood · 2023Article
- Review
- The APC-EPCR-PAR1 axis in sickle cell disease.Frontiers in medicine · 2023Review
- GB83, an Agonist of PAR2 with a Unique Mechanism of Action Distinct from Trypsin and PAR2-AP.International journal of molecular sciences · 2022Article
- Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities.European journal of immunology · 2022Review
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza A virus and coronavirus.Journal of thrombosis and haemostasis : JTH · 2021Review
- Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of blood coagulation and endothelial inflammation are hallmarks of respiratory infections with RNA viruses that contribute significantly to the morbidity and mortality of patients with severe disease. We investigated how signaling by coagulation proteases affects the quality and extent of the response to the TLR3-ligand poly(I:C) in human endothelial cells. Genome-wide RNA profiling documented additive and synergistic effects of thrombin and poly(I:C) on the expression level of many genes. The most significantly active genes exhibiting synergistic induction by costimulation with thrombin and poly(I:C) included the key mediators of 2 critical biological mechanisms known to promote endothelial thromboinflammatory functions: the initiation of blood coagulation by tissue factor and the control of leukocyte trafficking by the endothelial-leukocyte adhesion receptors E-selectin (gene symbol, SELE) and VCAM1, and the cytokines and chemokines CXCL8, IL-6, CXCL2, and CCL20. Mechanistic studies have indicated that synergistic costimulation with thrombin and poly(I:C) requires proteolytic activation of protease-activated receptor 1 (PAR1) by thrombin and transactivation of PAR2 by the PAR1-tethered ligand. Accordingly, a small-molecule PAR2 inhibitor suppressed poly(I:C)/thrombin-induced leukocyte-endothelial adhesion, cytokine production, and endothelial tissue factor expression. In summary, this study describes a positive feedback mechanism by which thrombin sustains and amplifies the prothrombotic and proinflammatory function of endothelial cells exposed to the viral RNA analogue, poly(I:C) via activation of PAR1/2.
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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 Socratic graph.