ArticleCirculation2023
Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.
Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 25 citations in OpenAlex.
- Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Article
- Emerging roles of the cGAS/STING pathway in cardiovascular diseases.The Journal of clinical investigation · 2026Review
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- NK-cell-derived exosomes exert antitumor potency via miR-140/XYLT1/HSPG2 axis.Cellular & molecular biology letters · 2026Article
- Calcific Aortopathy in Response to Aging and Injury.Circulation · 2026Review
- Establishment of a novel brainstem ischemic dysphagia model: single-cell sequencing reveals the molecular mechanisms underlying mPES intervention.Journal of neuroengineering and rehabilitation · 2025Article
- The Pathogenic Roles of Local Vitamin D Metabolism Defect in Valve Inflammation and Calcification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies.Biomedicines · 2025Review
- Impact of cardiovascular comorbidities on echocardiographic parameters in aortic stenosis.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2025Article
- Neutrophil Percentage to Albumin Ratio Is Associated With In-Hospital Mortality in Patients With Acute Type A Aortic Dissection.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Establishment and characterization of a novel immortalized human aortic valve interstitial cell line.Scientific reports · 2025Article
- Calcific aortic stenosis: omics-based target discovery and therapy development.European heart journal · 2025Review
- Efficacy and Potential Mechanisms of Yi-Ping Lin Circum-Knee Acupuncture in the Treatment of Knee Osteoarthritis.Journal of pain research · 2025Article
- Review
- Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies.Annals of medicine and surgery (2012) · 2024Review
- Identification of Circulating Inflammatory Proteins Associated with Calcific Aortic Valve Stenosis by Multiplex Analysis.Cardiovascular toxicology · 2024Observational
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.Journal of the American Heart Association · 2024Article
- Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.Journal of cardiovascular development and disease · 2024Review
Corrections and comments
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Authors and funding
44 authors at 9 institutions in 9 countries.
Funding
Abstract
backgroundCalcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling.
methodsHuman valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (
resultsHere, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that
conclusionsThis study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.
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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.