ArticleArthritis & rheumatology (Hoboken, N.J.)2016
ApoE Receptor 2 Mediation of Trophoblast Dysfunction and Pregnancy Complications Induced by Antiphospholipid Antibodies in Mice.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 76 citations in OpenAlex.
- EVT-Derived Migrasomes Provide Mechanistic Insights Into Antiphospholipid Syndrome-Associated Recurrent Miscarriage.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Reelin regulates the migration and differentiation of extravillous trophoblastic cells.Biological research · 2026Article
- Ubiquitin-proteasome system: a potential participant and therapeutic target in antiphospholipid syndrome.Frontiers in immunology · 2025Review
- Impaired implantation as a major upstream pathway of preeclampsia: a narrative synthesis of mechanistic, epidemiological and biomarker evidence.Frontiers in reproductive health · 2025Review
- B Cell Responses to the Placenta and Fetus.Annual review of pathology · 2025Review
- Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells.iScience · 2024Article
- Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults.Journal of clinical medicine · 2024Review
- Bta-miR-665 improves bovine blastocyst development through its influence on microtubule dynamics and apoptosis.Frontiers in genetics · 2024Article
- Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells.Biomedicines · 2023Article
- Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.Journal of nanobiotechnology · 2023Article
- 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
- Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies?Biomedicines · 2022Article
- Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome.Journal of cellular and molecular medicine · 2022Article
- Antiphospholipid Antibodies Increase Endometrial Stromal Cell Decidualization, Senescence, and Inflammation via Toll-like Receptor 4, Reactive Oxygen Species, and p38 MAPK Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome.Seminars in immunopathology · 2022Review
- Human Placental Intracellular Cholesterol Transport: A Focus on Lysosomal and Mitochondrial Dysfunction and Oxidative Stress.Antioxidants (Basel, Switzerland) · 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
- Review
- Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome.Circulation research · 2021Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivePregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine whether the low-density lipoprotein receptor family member apolipoprotein E receptor 2 (ApoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL.
methodsPlacental and trophoblast ApoER2 expression was evaluated by immunohistochemistry and immunoblotting. Normal human IgG and aPL were purified from healthy individuals and APS patients, respectively. The role of ApoER2 in aPL-induced changes in trophoblast proliferation and migration and in kinase activation was assessed using RNA interference in HTR-8/SVneo cells. The participation of ApoER2 in aPL-induced pregnancy loss and IUGR was evaluated in pregnant ApoER2(+/+) and ApoER2(-/-) mice injected with aPL or normal human IgG.
resultsWe found that ApoER2 is abundant in human and mouse placental trophoblasts and in multiple trophoblast-derived cell lines, including HTR-8/SVneo cells. ApoER2 and its interaction with the cell surface protein β2 -glycoprotein I were required for aPL-induced inhibition of cultured trophoblast proliferation and migration. In parallel, aPL antagonism of Akt kinase activation by epidermal growth factor in trophoblasts was mediated by ApoER2. Furthermore, in a murine passive-transfer model of pregnancy complications of APS, ApoER2(-/-) mice were protected from both aPL-induced fetal loss and aPL-induced IUGR.
conclusionApoER2 plays a major role in the attenuation of trophoblast function by aPL, and the receptor mediates aPL-induced pregnancy complications in vivo in mice. ApoER2-directed interventions can now potentially be developed to combat the pregnancy complications associated with APS.
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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.