ArticleArteriosclerosis, thrombosis, and vascular biology2015
Fibronectin Splicing Variants Containing Extra Domain A Promote Atherosclerosis in Mice Through Toll-Like Receptor 4.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Exploring associations between estrogen and gene candidates identified by coronary artery disease genome-wide association studies.Frontiers in cardiovascular medicine · 2025Pooled it
- The Role of Myeloid Differentiation Factor 2 in Stroke: Mechanisms and Therapeutic Potential.Biomolecules · 2025Review
- Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics.International journal of molecular sciences · 2025Article
- Smooth Muscle Cell-Derived Fibronectin Promotes an Atheroprotective Smooth Muscle Cell Phenotype Associated With Altered NO-cGMP Signaling.Journal of the American Heart Association · 2025Article
- Article
- Including microbiome information in a multi-trait genomic evaluation: a case study on longitudinal growth performance in beef cattle.Genetics, selection, evolution : GSE · 2024Article
- The role of splicing events in the inflammatory response of atherosclerosis: molecular mechanisms and modulation.Frontiers in immunology · 2024Review
- Targeting Neutrophil α9 Improves Functional Outcomes After Stroke in Mice With Obesity-Induced Hyperglycemia.Stroke · 2023Article
- Review
- Induction of pro-inflammatory genes by fibronectin DAMPs in three fibroblast cell lines: Role of TAK1 and MAP kinases.PloS one · 2023Article
- Different roles of endothelial cell-derived fibronectin and plasma fibronectin in endothelial dysfunction.Turkish journal of medical sciences · 2023Article
- Article
- Fibronectin containing alternatively spliced extra domain A interacts at the central and c-terminal domain of Toll-like receptor-4.Scientific reports · 2022Article
- Myeloid Cell PKM2 Deletion Enhances Efferocytosis and Reduces Atherosclerosis.Circulation research · 2022Article
- Megakaryocyte Diversity in Ontogeny, Functions and Cell-Cell Interactions.Frontiers in oncology · 2022Article
- Elevated plasma EDA fibronectin in primary myelofibrosis is determined by high allele burden ofFrontiers in oncology · 2022Article
- Bioinformatics and Machine Learning Methods to Identify FN1 as a Novel Biomarker of Aortic Valve Calcification.Frontiers in cardiovascular medicine · 2022Article
- Comprehensive functional core microbiome comparison in genetically obese and lean hosts under the same environment.Communications biology · 2021Article
- Macrophages and Extracellular Matrix in Breast Cancer: Partners in Crime or Protective Allies?Frontiers in oncology · 2021Review
- Fibronectin 1 activates WNT/β-catenin signaling to induce osteogenic differentiation via integrin β1 interaction.Laboratory investigation; a journal of technical methods and pathology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCellular fibronectin containing extra domain A (EDA(+)-FN) is abundant in the arteries of patients with atherosclerosis. Several in vitro studies suggest that EDA(+)-FN interacts with Toll-like receptor 4 (TLR4). We tested the hypothesis that EDA(+)-FN exacerbates atherosclerosis through TLR4 in a clinically relevant model of atherosclerosis, the apolipoprotein E-deficient (Apoe(-/-)) mouse. APPROACH AND
resultsThe extent of atherosclerosis was evaluated in whole aortae and cross sections of the aortic sinus in male and female EDA(-/-)Apoe(-/-) mice (which lack EDA(+)-FN), EDA(fl/fl)Apoe(-/-) mice (which constitutively express EDA(+)-FN), and control Apoe(-/-) mice fed a high-fat Western diet for 14 weeks. Irrespective of sex, EDA(fl/fl)Apoe(-/-) mice exhibited a 2-fold increase in atherosclerotic lesions (aorta and aortic sinus) and macrophage content within plaques, whereas EDA(-/-)Apoe(-/-) mice exhibited reduced atherosclerotic lesions (P<0.05 versus Apoe(-/-), n=10-12 mice/group), although cholesterol and triglyceride levels and circulating leukocytes were similar. Genetic ablation of TLR4 partially reversed atherosclerosis exacerbation in EDA(fl/fl)Apoe(-/-) mice (P<0.05) but had no effect on atherosclerotic lesions in EDA(-/-)Apoe(-/-) mice. Purified cellular FN, which contains EDA, potentiated dose-dependent NFκB-mediated inflammation (increased phospho-NFκB p65/NFκB p65, tumor necrosis factor-α, and interleukin-1β) in bone marrow-derived macrophages from EDA(-/-)Apoe(-/-) mice but not from EDA(-/-)TLR4(-/-)Apoe(-/-) mice. Finally, using immunohistochemistry, we provide evidence for the first time that EDA(+)-FN colocalizes with macrophage TLR4 in murine aortic lesions and human coronary artery atherosclerotic plaques.
conclusionsOur findings reveal that TLR4 signaling contributes to EDA(+)-FN-mediated exacerbation of atherosclerosis. We suggest that EDA(+)-FN could be a therapeutic target in atherosclerosis.
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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.