ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Autoantibody-mediated IL-6-dependent endothelin-1 elevation underlies pathogenesis in a mouse model of preeclampsia.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed, 94 citations in OpenAlex.
- Exploring the role of exosomal MicroRNAs as potential biomarkers in preeclampsia.Frontiers in immunology · 2024Review
- Preliminary evidence that blocking the uptake of placenta-derived preeclamptic extracellular vesicles protects the vascular endothelium and prevents vasoconstriction.Scientific reports · 2023Article
- Endothelin-1 in Health and Disease.International journal of molecular sciences · 2023Review
- HMGB1: a double-edged sword and therapeutic target in the female reproductive system.Frontiers in immunology · 2023Review
- Structures and functions of cilia during vertebrate embryo development.Molecular reproduction and development · 2022Review
- Echinochrome A Reverses Kidney Abnormality and Reduces Blood Pressure in a Rat Model of Preeclampsia.Marine drugs · 2022Article
- Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model.Antioxidants (Basel, Switzerland) · 2022Article
- The association of posterior reversible encephalopathy syndrome with COVID-19: A systematic review.Annals of medicine and surgery (2012) · 2021Review
- Epigenetic processes during preeclampsia and effects on fetal development and chronic health.Clinical science (London, England : 1979) · 2021Review
- Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation.Kidney international reports · 2020Article
- The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia.Current hypertension reports · 2018Review
- Preeclampsia: From Inflammation to Immunoregulation.Clinical medicine insights. Blood disorders · 2018Article
- Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.Lipids in health and disease · 2017Article
- Effect of a black cumin (Journal of Taibah University Medical Sciences · 2017Article
- The Endothelin Type A Receptor as a Potential Therapeutic Target in Preeclampsia.International journal of molecular sciences · 2017Review
- Article
- The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia.Therapeutic advances in cardiovascular disease · 2016Review
- Identifying immune mechanisms mediating the hypertension during preeclampsia.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Understanding mechanisms of hypertension in systemic lupus erythematosus.Therapeutic advances in cardiovascular disease · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy. Elevated circulating endothelin-1 (ET-1) is associated with the disease. However the molecular basis of increased ET-1 production and its role in PE are unknown. This study aimed to investigate the causative factors, pathological role of elevated ET-1 production in PE, and the underlying mechanisms. In this study, we found that IgG from women with PE, in contrast to IgG from normotensive pregnant women, induced preproET-1 mRNA expression via angiotensin II type 1 receptor activation in kidneys and placentas in pregnant mice. The ET-A receptor-specific antagonist BQ123 significantly attenuated autoantibody-induced hypertension, proteinuria, and renal damage in pregnant mice, demonstrating that autoantibody-induced ET-1 production contributes to pathophysiology. Mechanistically, we discovered that IL-6 functioned downstream of TNF-α signaling, contributing to increased ET-1 production in pregnant mice. IL-6 blockade inhibited preeclamptic features in autoantibody-injected pregnant mice. Extending the data to human studies, we found that IL-6 was a key cytokine underlying ET-1 induction mediated by IgG from women with PE in human placental villous explants and that endothelial cells are a key source of ET-1. Overall, we provide human and mouse studies showing that angiotensin II type I receptor-agonistic autoantibody is a novel causative factor responsible for elevated ET-1 production and that increased TNF-α/IL-6 signaling is a key mechanism underlying increased ET-1 production and subsequent maternal features. Significantly, our findings revealed novel factors and signaling cascades involved in ET-1 production, subsequent disease symptom development, and possible therapeutic intervention in the management of PE.
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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.