ArticleJournal of molecular medicine (Berlin, Germany)2017
Wnt5a is elevated in heart failure and affects cardiac fibroblast function.
Article in Journal of molecular medicine (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 83 citations in OpenAlex.
- The intersection of disorders of sex development and cardiovascular diseases.Biology of sex differences · 2026Review
- Assessments of Wnt/JAK-STAT Signaling Pathway in Relation to Sfrp5 Among Patients with Cardiac Diseases.International journal of molecular sciences · 2025Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- Wnt5a-mediated Adipo-Cardiac Interorgan Communication in HFpEF.bioRxiv : the preprint server for biology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Omentin-1 as a promising biomarker and therapeutic target in hypertension and heart failure: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting Wnt Pathways with Small Molecules as New Approach in Cardiovascular Disease.Current cardiology reviews · 2025Review
- Mechanism and research progress of MAPK signaling pathway in myocardial fibrosis.Frontiers in cardiovascular medicine · 2025Review
- Wnt Signaling Inhibitors as Therapeutic Approach in Ischemic Heart Disease.Molecules (Basel, Switzerland) · 2024Review
- Clinical impact of Wnt5a expression on persistence of acute kidney injury in patients with urosepsis.Renal failure · 2024Article
- Review
- Article
- Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.The Journal of clinical investigation · 2024Article
- Patient-specific iPSC-derived cardiomyocytes reveal aberrant activation of Wnt/β-catenin signaling in SCN5A-related Brugada syndrome.Stem cell research & therapy · 2023Article
- Article
- Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications.Nature reviews. Cardiology · 2022Review
- Elucidating the role of circNFIB in myocardial fibrosis alleviation by endogenous sulfur dioxide.BMC cardiovascular disorders · 2022Article
- Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload.Cell death & disease · 2021Article
- WNT/β-Catenin Signaling Promotes TGF-β-Mediated Activation of Human Cardiac Fibroblasts by Enhancing IL-11 Production.International journal of molecular sciences · 2021Article
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt signaling is dysregulated in heart failure (HF) and may promote cardiac hypertrophy, fibrosis, and inflammation. Blocking the Wnt ligand Wnt5a prevents HF in animal models. However, the role of Wnt5a in human HF and its functions in cardiac cells remain unclear. Here, we investigated Wnt5a regulation in HF patients and its effects on primary mouse and human cardiac fibroblasts. Serum Wnt5a was elevated in HF patients and associated with hemodynamic, neurohormonal, and clinical measures of disease severity. In failing human hearts, Wnt5a protein correlated with interleukin (IL)-6 and tissue inhibitor of metalloproteinase (TIMP)-1. Wnt5a messenger RNA (mRNA) levels were markedly upregulated in failing myocardium and both mRNA and protein levels declined following left ventricular assist device therapy. In primary mouse and human cardiac fibroblasts, recombinant Wnt5a dose-dependently upregulated mRNA and protein release of IL-6 and TIMP-1. Wnt5a did not affect β-catenin levels, but activated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Importantly, inhibition of ERK1/2 activation attenuated Wnt5a-induced release of IL-6 and TIMP-1. In conclusion, our results show that Wnt5a is elevated in the serum and myocardium of HF patients and is associated with measures of progressive HF. Wnt5a induces IL-6 and TIMP-1 in cardiac fibroblasts, which might promote myocardial inflammation and fibrosis, and thereby contribute to HF progression. KEY MESSAGES: • Wnt5a is elevated in serum and myocardium of HF patients and is associated with measures of progressive HF. • In cardiac fibroblasts, Wnt5a upregulates interleukin (IL)-6 and tissue inhibitor of metalloproteinase (TIMP)-1 through the ERK pathway. • Wnt5a-mediated effects might promote myocardial inflammation and fibrosis, and thereby contribute to HF progression.
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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.