ArticleHypertension (Dallas, Tex. : 1979)2015
Profibrotic Role for Interleukin-4 in Cardiac Remodeling and Dysfunction.
Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 110 citations in OpenAlex.
- Impact of a durable left ventricular assist device on inflammation and cardiac remodelling in subjects with advanced heart failure.Open heart · 2026Observational
- Exploring pathogenetic mechanisms in subglottic stenosis: A narrative review toward an integrated molecular classification.Multidisciplinary respiratory medicine · 2026Article
- Long-term temporal stability of circulating proteins in older adults.Nature communications · 2026Article
- Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells.Cell and tissue research · 2026Article
- Depression of tryptophan may contribute to adverse effects of naproxen.Nature communications · 2026Article
- Integration of transcriptome and mendelian randomization analyses to explore the molecular mechanisms of atrial fibrillation.Journal of cardiothoracic surgery · 2026Article
- Sotagliflozin Enhances Left Ventricular Function and Myocardial Perfusion in Chronic Myocardial Ischemia Through Metabolic and Redox Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Aerobic exercise training attenuates cardiac inflammation and fibrosis in mice with type 2 diabetes and inhibits the advanced glycation end products pathway.Diabetology & metabolic syndrome · 2026Article
- Unbiased assessment of 2-arachidonoylglycerol in cardiovascular inflammation.Scientific reports · 2025Article
- Rewiring the scar: translational advances in cardiac fibrosis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Macrophage-Derived CCL24 Promotes Cardiac Fibrosis Via Fibroblast CCR3.Circulation research · 2025Article
- Immune and Vascular Function in Cardiometabolic Disorders: Interplay With Sex Differences and Impact on Incretin Therapy.Acta physiologica (Oxford, England) · 2025Review
- The Renin-Angiotensin-Aldosterone System (RAAS): Beyond Cardiovascular Regulation.Veterinary sciences · 2025Review
- Radiation-Induced Cardiac Remodeling: Mechanisms and Therapeutic Approaches.Cardiovascular toxicology · 2025Review
- Targeting inhibition of the inflammatory response: advances in the treatment of myocardial fibrosis with natural medicine and active ingredients.Frontiers in cardiovascular medicine · 2025Review
- Myrcene enhances the cardioprotective effect through matrix remodelling in an experimental model of heart failure.Archives of medical science : AMS · 2025Article
- Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles activate CD4+ T cells from Chagas cardiomyopathy patients and are associated with ventricular dysfunction.Frontiers in immunology · 2025Article
- The immunology of diabetic cardiomyopathy.Frontiers in endocrinology · 2025Review
- Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs.bioRxiv : the preprint server for biology · 2024Article
- Indoxyl sulphate-initiated activation of cardiac fibroblasts is modulated by aryl hydrocarbon receptor and nuclear factor-erythroid-2-related factor 2.Journal of cellular and molecular medicine · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Elevated interleukin-4 (IL-4) levels are associated with cardiac fibrosis in hypertension and heart failure in both patients and experimental animals. We hypothesized that chronically elevated IL-4 induces cardiac fibrosis, resulting in a predisposition of the heart to angiotensin II-induced damage. Wild-type Balb/c (WT, high circulating IL-4) and IL-4-deficient Balb/c mice (IL-4(-/-)) were used. WT mice exhibited cardiac fibrosis (evidenced by an increase in expression of procollagen genes/interstitial collagen fraction), enlarged left ventricle chamber, and declined cardiac function associated with a greater number of mast cells and macrophages in the heart compared with IL-4(-/-). In contrast, IL-4(-/-) mice had normal cardiac architecture/function while showing a 57.9% reduction in heart interstitial collagen compared with WT, despite elevated proinflammatory cytokines in heart tissue. In response to angiotensin II administration, IL-4(-/-) had reduced interstitial myocardial fibrosis and were protected from developing dilated cardiomyopathy, which was seen in WT mice. This was associated with increased macrophage infiltration into the hearts of WT mice, despite a similar degree of hypertension and increased cardiac transforming growth factor-β1 in both groups. In vitro data demonstrated that IL-4 upregulates procollagen genes and stimulates collagen production in mouse cardiac fibroblasts. This process is mediated by signal transducer and activator of transcription 6 signaling pathway via IL-4 receptor alpha. This study not only establishes a causal relationship between IL-4 and cardiac fibrosis/dysfunction, but also reveals a critical role for IL-4 in angiotensin II-induced cardiac damage. IL-4 could serve as an additional target for the treatment of cardiac fibrosis.
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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.