ArticleThe Journal of biological chemistry2011
A novel role of endothelin-1 in linking Toll-like receptor 7-mediated inflammation to fibrosis in congenital heart block.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00074373 (The Research Registry for Neonatal Lupus), which is not on this map. Cited by 36 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.
The trial behind it
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.
The Research Registry for Neonatal Lupus
Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Ro60 requires Y3 RNA for cell surface exposure and inflammation associated with cardiac manifestations of neonatal lupus.Journal of immunology (Baltimore, Md. : 1950) · 2013Trial
- TLR7 inhibition limits cardiac ischemic injury by disrupting ITGAM-dependent immune-endothelial interaction.bioRxiv : the preprint server for biology · 2026Article
- Rewiring the scar: translational advances in cardiac fibrosis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Maternal Immune Activation: Implications for Congenital Heart Defects.Clinical reviews in allergy & immunology · 2025Review
- Obstructive Sleep Apnea and Hypertensive Heart Disease: From Pathophysiology to Therapeutics.Reviews in cardiovascular medicine · 2023Review
- The EDN1/EDNRA/β‑arrestin axis promotes colorectal cancer progression by regulating STAT3 phosphorylation.International journal of oncology · 2023Article
- NLRP3 activation contributes to endothelin-1-induced erectile dysfunction.Journal of cellular and molecular medicine · 2023Article
- The role of endothelin and RAS/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications.Arthritis research & therapy · 2022Review
- Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages.Mucosal immunology · 2022Article
- Third Trimester Fetal Heart Rates in Antibody-Mediated Complete Heart Block Predict Need for Neonatal Pacemaker Placement.Pediatric cardiology · 2022Article
- Cardiac Macrophages and Their Effects on Arrhythmogenesis.Frontiers in physiology · 2022Review
- Crosstalk Between Cardiac Cells and Macrophages Postmyocardial Infarction: Insights fromTissue engineering. Part B, Reviews · 2021Review
- Cardiac fibrosis.Cardiovascular research · 2021Review
- A Broader Perspective on Anti-Ro Antibodies and Their Fetal Consequences-A Case Report and Literature Review.Diagnostics (Basel, Switzerland) · 2020Review
- Pathophysiology of Hypertensive Heart Disease: Beyond Left Ventricular Hypertrophy.Current hypertension reports · 2020Review
- Use of antenatal fluorinated corticosteroids in management of congenital heart block: Systematic review and meta-analysis.European journal of obstetrics & gynecology and reproductive biology: X · 2019Review
- Prenatal diagnosis and management of congenital complete heart block.Birth defects research · 2019Review
- Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus.Annals of the rheumatic diseases · 2018Article
- Pulmonary artery smooth muscle cell HIF-1α regulates endothelin expression via microRNA-543.American journal of physiology. Lung cellular and molecular physiology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Autoimmune associated congenital heart block (CHB) may result from pathogenic cross-talk between inflammatory and profibrosing pathways. Incubation of macrophages with immune complexes (IC) composed of Ro60, a target of the pathologic maternal autoantibodies necessary for CHB, hY3 ssRNA, and affinity-purified anti-Ro60 antibody induces the Toll-like receptor 7 (TLR7)-dependent generation of supernatants that provoke a fibrosing phenotype in human fetal cardiac fibroblasts. We show herein that these cells are a major source of TGFβ and that endothelin-1 (ET-1) is one of the key components responsible for the profibrosing effects generated by stimulated macrophages. Supernatants from macrophages incubated with IC induced the fibroblast secretion of TGFβ, which was inhibited by treating the macrophages with an antagonist of TLR7. Under the same conditions, the induced fibroblast secretion of TGFβ was decreased by inhibitors of the ET-1 receptors ETa or ETb or by an anti-ET-1 antibody but not by an isotype control. Exogenous ET-1 induced a profibrosing phenotype, whereas fibroblasts transfected with either ETa or ETb siRNA were unresponsive to the profibrosing effects of the IC-generated macrophage supernatants. Immunohistochemistry of the hearts from two fetuses dying with CHB revealed the presence of ET-1-producing mononuclear cells in the septal region in areas of calcification and fibrosis. In conclusion, these data support a novel role of ET-1 in linking TLR7 inflammatory signaling to subsequent fibrosis and provide new insight in considering therapeutics for CHB.
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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.