ArticleBlood2021
IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Colchicine Protects Against Sickle Cell Related Cardiomyopathy: Evidence of the Novel Role of Inflammaging.Antioxidants (Basel, Switzerland) · 2026Article
- Contactin-2 mitigates heart failure and cardiac remodeling via regulation of NUPR1 and ferroptosis.Biology direct · 2026Article
- Plasma proteome signatures are predictive of mortality in sickle cell disease.Blood advances · 2026Article
- Sodium Channel Isoform Diversity Underlies Chamber-Specific Cardiac Excitability.Circulation research · 2026Article
- Exploring Affordable Curative Therapy for Sickle Cell Disease in Africa: A Comprehensive Overview.American journal of hematology · 2026Review
- Effect of Red Blood Cell Transfusion on Inflammatory and Angiogenic Pathways in Patients With Sickle Cell Disease.American journal of hematology · 2026Article
- Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance.EMBO reports · 2026Article
- Sickle cell related cardiomyopathy and cardiovascular autonomic dysfunction.Frontiers in cardiovascular medicine · 2026Review
- Arrhythmogenic Mechanisms of Novel Biomarkers in Cardiac Electrophysiology.Cardiology research and practice · 2026Review
- Sickle Cell Diastolic Cardiomyopathy and Mortality Risk: A Novel Echocardiographic Framework for Prognostic Stratification.American journal of hematology · 2025Article
- Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.Haematologica · 2025Article
- 17(R)-Resolvin D1 protects against sickle cell-related inflammatory cardiomyopathy in humanized mice.Blood · 2025Article
- Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease.British journal of haematology · 2025Article
- Atrial arrhythmia in adults with sickle cell anemia: a missing link toward understanding and preventing strokes.Blood advances · 2024Article
- Obesity Arrhythmias: Role of IL-6 Trans-Signaling.International journal of molecular sciences · 2024Review
- STAT4 Mediates IL-6 Trans-Signaling Arrhythmias in High Fat Diet Guinea Pig Heart.International journal of molecular sciences · 2024Article
- Interleukin‑18 binding protein: Biological properties and roles in human and animal immune regulation (Review).Biomedical reports · 2024Review
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Ventricular arrhythmias in sickle cell anemia.Blood · 2023Article
- SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy.Signal transduction and targeted therapy · 2023Article
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28 authors at 12 institutions in 2 countries.
Funding
Abstract
Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.
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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.