ArticleJournal of the American Heart Association2020
Syndecan-4 Protects the Heart From the Profibrotic Effects of Thrombin-Cleaved Osteopontin.
Article in Journal of the American Heart Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 47 citations in OpenAlex.
- Plasma proteomics of cerebrovascular disease, cognitive decline, and clinical outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting thrombin with hirudin alleviates paraquat-induced pulmonary fibrosis via the PAR-1-mediated TGF-β1 pathway.Histology and histopathology · 2026Article
- Osteopontin-expressing valvular interstitial cell subpopulation as a driver of extracellular matrix remodeling in aortic valve disease.Frontiers in cardiovascular medicine · 2026Article
- Dual roles of syndecan-4 in regulating chicken fibrosisFrontiers in physiology · 2026Article
- Shed Syndecan-4 and Its Possible Roles in Osteoarthritis.Biomedicines · 2025Review
- Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.Circulation research · 2025Article
- The immune duality of osteopontin and its therapeutic implications for kidney transplantation.Frontiers in immunology · 2025Review
- Matrisome remodeling in the myocardium of hypertrophic cardiomyopathy; novel targets for molecular diagnostics.Frontiers in cell and developmental biology · 2025Review
- Cardiac implications of chicken wooden breast myopathy.Frontiers in physiology · 2025Article
- Temporal trajectory and left ventricular ejection fraction association of eight circulating biomarkers in first acute myocardial infarction patients: a 12-month prospective cohort study.European heart journal open · 2024Article
- Osteopontin as a Biomarker in Interstitial Lung Diseases.Biomedicines · 2024Article
- Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.Molecular biology reports · 2024Article
- APP-CD74 axis mediates endothelial cell-macrophage communication to promote kidney injury and fibrosis.Frontiers in pharmacology · 2024Article
- Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality.PloS one · 2024Article
- Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet.Frontiers in cardiovascular medicine · 2024Article
- Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.Nature communications · 2023Article
- Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management.Reviews in endocrine & metabolic disorders · 2023Review
- Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan-4 Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Syndecan-4 as a genetic determinant of the metabolic syndrome.Diabetology & metabolic syndrome · 2023Article
- Review
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
Background Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling mechanisms are not well understood. Herein, we examine the effect of thrombin-cleaved osteopontin on fibrosis in the heart and explore the role of syndecan-4 in regulating cleavage of osteopontin. Methods and Results Osteopontin was upregulated and cleaved by thrombin in the pressure-overloaded heart of mice subjected to aortic banding. Cleaved osteopontin was higher in plasma from patients with aortic stenosis receiving crystalloid compared with blood cardioplegia, likely because of less heparin-induced inhibition of thrombin. Cleaved osteopontin and the specific osteopontin peptide sequence RGDSLAYGLR that is exposed after thrombin cleavage both induced collagen production in cardiac fibroblasts. Like osteopontin, the heparan sulfate proteoglycan syndecan-4 was upregulated after aortic banding. Consistent with a heparan sulfate binding domain in the osteopontin cleavage site, syndecan-4 was found to bind to osteopontin in left ventricles and cardiac fibroblasts and protected osteopontin from cleavage by thrombin. Shedding of the extracellular part of syndecan-4 was more prominent at later remodeling phases, at which time levels of cleaved osteopontin were increased. Conclusions Thrombin-cleaved osteopontin induces collagen production by cardiac fibroblasts. Syndecan-4 protects osteopontin from cleavage by thrombin, but this protection is lost when syndecan-4 is shed in later phases of remodeling, contributing to progression of cardiac fibrosis.
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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.