ArticleThe Journal of clinical investigation2011
Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 192 citations in OpenAlex.
- Animal models of antiphospholipid syndrome.Frontiers in immunology · 2026Review
- Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome.Journal of translational autoimmunity · 2025Article
- Microvascular Endothelial Cells License APS Vasculopathy Through YAP1- and CCN2-Mediated Signaling.Circulation · 2025Article
- 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
- Extracellular Vesicles Analysis as Possible Signatures of Antiphospholipid Syndrome Clinical Features.International journal of molecular sciences · 2025Article
- Review
- Effect of PCSK9 Inhibitors on Regulators of Lipoprotein Homeostasis, Inflammation and Coagulation.Biomedicines · 2025Article
- Antiphospholipid Syndrome: A Comprehensive Clinical Review.Journal of clinical medicine · 2025Review
- Impaired implantation as a major upstream pathway of preeclampsia: a narrative synthesis of mechanistic, epidemiological and biomarker evidence.Frontiers in reproductive health · 2025Review
- Antiphospholipid antibodies induce endothelial procoagulant activity and release of extracellular vesicles independently of a second hit.Frontiers in immunology · 2025Article
- Mechanism of antiphospholipid antibody-mediated thrombosis in antiphospholipid syndrome.Frontiers in immunology · 2025Review
- ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Expression, purification and characterization of phosphatidylserine-targeting antibodies for biochemical and therapeutic applications.Methods in cell biology · 2025Article
- Current Prognostic Biomarkers for Abdominal Aortic Aneurysm: A Comprehensive Scoping Review of the Literature.Biomolecules · 2024Article
- Rethinking antiphospholipid syndrome to guide future management and research.Nature reviews. Rheumatology · 2024Review
- A single intravenous reelin injection restores corticosterone-induced neurochemical and behavioral alterations in dams during the post-partum period.Frontiers in molecular neuroscience · 2024Article
- Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome.Frontiers in immunology · 2024Review
- Proposal of a novel cardiovascular risk prediction score in lupus nephritis.Frontiers in immunology · 2024Article
- Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells.Biomedicines · 2023Article
- Oxidative Stress as a Regulatory Checkpoint in the Production of Antiphospholipid Autoantibodies: The Protective Role of NRF2 Pathway.Biomolecules · 2023Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to β2 glycoprotein I (β2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms. Here we show that in mice both of these processes are caused by the inhibition of eNOS. In studies of cultured human, bovine, and mouse endothelial cells, the promotion of monocyte adhesion by aPL entailed decreased bioavailable NO, and aPL fully antagonized eNOS activation by diverse agonists. Similarly, NO-dependent, acetylcholine-induced increases in carotid vascular conductance were impaired in aPL-treated mice. The inhibition of eNOS was caused by antibody recognition of domain I of β2GPI and β2GPI dimerization, and it was due to attenuated eNOS S1179 phosphorylation mediated by protein phosphatase 2A (PP2A). Furthermore, LDL receptor family member antagonism with receptor-associated protein (RAP) prevented aPL inhibition of eNOS in cell culture, and ApoER2-/- mice were protected from aPL inhibition of eNOS in vivo. Moreover, both aPL-induced increases in leukocyte-endothelial cell adhesion and thrombus formation were absent in eNOS-/- and in ApoER2-/- mice. Thus, aPL-induced leukocyte-endothelial cell adhesion and thrombosis are caused by eNOS antagonism, which is due to impaired S1179 phosphorylation mediated by β2GPI, apoER2, and PP2A. Our results suggest that novel therapies for APS can now be developed targeting these mechanisms.
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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.