ArticleArteriosclerosis, thrombosis, and vascular biology2014
Alternative splicing of endothelial fibronectin is induced by disturbed hemodynamics and protects against hemorrhage of the vessel wall.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Association of Matrix Metalloproteinase 9 and Cellular Fibronectin and Outcome in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.Frontiers in neurology · 2020Pooled it
- Splicing of fibronectin gene contribute to the aneurysmal dilatation of arteriovenous fistula.Renal failure · 2026Article
- Multiomic Reference Map of Endothelial Mechanosensitive Pathways Under Athero- and Erosion-Prone Flow.Journal of the American Heart Association · 2026Article
- Endothelial Elavl1 Is Required for CD8 T-Cell Persistence in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- 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
- Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024Review
- Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR.bioRxiv : the preprint server for biology · 2024Article
- Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Angiogenic adipokine C1q-TNF-related protein 9 ameliorates myocardial infarction via histone deacetylase 7-mediated MEF2 activation.Science advances · 2022Article
- Identification of splice regulators of fibronectin-EIIIA and EIIIB by direct measurement of exon usage in a flow-cytometry based CRISPR screen.Scientific reports · 2021Article
- Mechanisms of Endothelial-to-Mesenchymal Transition Induction by Extracellular Matrix Components in Pulmonary Fibrosis.Bulletin of experimental biology and medicine · 2021Article
- MEF2 (Myocyte Enhancer Factor 2) Is Essential for Endothelial Homeostasis and the Atheroprotective Gene Expression Program.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Alternative Splicing of FN (Fibronectin) Regulates the Composition of the Arterial Wall Under Low Flow.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- TMAO-Activated Hepatocyte-Derived Exosomes Impair AngiogenesisFrontiers in cell and developmental biology · 2021Article
- Tandem Mass Tag-Based Quantitative Proteomic Analysis Reveals Pathways Involved in Brain Injury Induced by Chest Exposure to Shock Waves.Frontiers in molecular neuroscience · 2021Article
- Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis.Journal of experimental & clinical cancer research : CR · 2020Review
- Role of Extracellular Matrix in Pathophysiology of Patent Ductus Arteriosus: Emphasis on Vascular Remodeling.International journal of molecular sciences · 2020Review
- Noninvasive imaging of tumor progression, metastasis, and fibrosis using a nanobody targeting the extracellular matrix.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci.American journal of physiology. Heart and circulatory physiology · 2019Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAbnormally low-flow conditions, sensed by the arterial endothelium, promote aneurysm rupture. Fibronectin (FN) is among the most abundant extracellular matrix proteins and is strongly upregulated in human aneurysms, suggesting a possible role in disease progression. Altered FN splicing can result in the inclusion of EIIIA and EIIIB exons, generally not expressed in adult tissues. We sought to explore the regulation of FN and its splicing and their possible roles in the vascular response to disturbed flow. APPROACH AND
resultsWe induced low and reversing flow in mice by partial carotid ligation and assayed FN splicing in an endothelium-enriched intimal preparation. Inclusion of EIIIA and EIIIB was increased as early as 48 hours, with negligible increases in total FN expression. To test the function of EIIIA and EIIIB inclusion, we induced disturbed flow in EIIIAB(-/-) mice unable to include these exons and found that they developed focal lesions with hemorrhage and hypertrophy of the vessel wall. Acute deletion of floxed FN caused similar defects in response to disturbed flow, consistent with a requirement for the upregulation of the spliced isoforms, rather than a developmental defect. Recruited macrophages promote FN splicing because their depletion by clodronate liposomes blocked the increase in endothelial EIIIA and EIIIB inclusion in the carotid model.
conclusionsThese results uncover a protective mechanism in the inflamed intima that develops under disturbed flow, by showing that splicing of FN mRNA in the endothelium, induced by macrophages, inhibits hemorrhage of the vessel wall.
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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.