ArticleThe Journal of clinical investigation2008
Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome-What is the evidence?Journal of thrombosis and haemostasis : JTH · 2021Pooled it
- Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss.The Cochrane database of systematic reviews · 2020Pooled it
- Combined Obstetric and Thrombotic Complications Are Associated with Features Suggestive of an Immune-Enriched Phenotype Among Women with Thrombotic Antiphospholipid Syndrome (APS).Diagnostics (Basel, Switzerland) · 2026Article
- Simvastatin Restores Uteroplacental Hemodynamics and Trophoblast Function in Obstetric Antiphospholipid Syndrome in a Placenta-on-a-Chip Model.Advanced healthcare materials · 2026Article
- Deciphering the Role and Mechanism of Decidual Monocyte-Derived Macrophage Infiltration in Obstetric Antiphospholipid Syndrome at Single-Cell Resolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Low-Molecular-Weight Heparin in Preeclampsia: Effects on Biomarkers and Prevention: A Narrative Review.Biomedicines · 2025Review
- Dexmedetomidine Reduces Chronic Stress-Related Thrombosis in a Mouse FeClFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.Blood · 2024Article
- The pathogenesis of obstetric APS: a 2023 update.Clinical immunology (Orlando, Fla.) · 2023Review
- Advances in the Pathophysiology of Thrombosis in Antiphospholipid Syndrome: Molecular Mechanisms and Signaling through Lipid Rafts.Journal of clinical medicine · 2023Review
- Dysregulated low-density granulocyte contributes to early spontaneous abortion.Frontiers in immunology · 2023Article
- GPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation.Nature communications · 2022Article
- The complement system and autoimmune diseases.Chronic diseases and translational medicine · 2022Review
- Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome.Seminars in immunopathology · 2022Review
- Article
- Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review.Journal of clinical medicine · 2022Review
- Effects of anti-beta 2-glycoprotein 1 antibodies and its association with pregnancy-related morbidity in antiphospholipid syndrome.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Review
- Immunological and physiopathological approach of COVID-19 in pregnancy.Archives of gynecology and obstetrics · 2021Review
- Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction.Journal of molecular cell biology · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Women with antiphospholipid syndrome (APS), a condition characterized by the presence of antiphospholipid antibodies (aPL), often suffer pregnancy-related complications, including miscarriage. We have previously shown that C5a induction of tissue factor (TF) expression in neutrophils contributes to respiratory burst, trophoblast injury, and pregnancy loss in mice treated with aPL. Here we analyzed how TF contributes to neutrophil activation and trophoblast injury in this model. Neutrophils from aPL-treated mice expressed protease-activated receptor 2 (PAR2), and stimulation of this receptor led to neutrophil activation, trophoblast injury, and fetal death. An antibody specific for human TF that has little impact on coagulation, but potently inhibits TF/Factor VIIa (FVIIa) signaling through PAR2, inhibited aPL-induced neutrophil activation in mice that expressed human TF. Genetic deletion of the TF cytoplasmic domain, which allows interaction between TF and PAR2, reduced aPL-induced neutrophil activation in aPL-treated mice. Par2-/- mice treated with aPL exhibited reduced neutrophil activation and normal pregnancies, which indicates that PAR2 plays an important role in the pathogenesis of aPL-induced fetal injury. We also demonstrated that simvastatin and pravastatin decreased TF and PAR2 expression on neutrophils and prevented pregnancy loss. Our results suggest that TF/FVIIa/PAR2 signaling mediates neutrophil activation and fetal death in APS and that statins may be a good treatment for women with aPL-induced pregnancy complications.
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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.