ArticleProceedings of the National Academy of Sciences of the United States of America2016
Critical role of RAGE and HMGB1 in inflammatory heart disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS.Reproductive biology and endocrinology : RB&E · 2016Pooled it
- Comparison of Cardioprotective Effects of Propofol versus Sevoflurane in Pediatric Living Donor Liver Transplantation.Annals of transplantation · 2020Trial
- Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent.Critical care (London, England) · 2016Trial
- Review
- Role of Cellular-Ferroptosis-Mediated HMGB1 Nuclear Translocation in Indium-Tin-Oxide-Nanoparticle-Induced Inflammatory Lung Injury.Environment & health (Washington, D.C.) · 2026Article
- Early Sustained High-Level HMGB1 and Poor Outcomes After Neonatal Congenital Cardiac Surgery with Cardiopulmonary Bypass.Pediatric cardiology · 2026Article
- Detection of Calpain-Mediated Beclin-1 Cleavage for Drug Discovery in Inflammatory Bowel Diseases.Cells · 2026Article
- Scoping review of preclinical and clinical studies on the role of HMGB1 in heart disease.NPJ cardiovascular health · 2026Article
- High mobility group box 1: DAMPening the danger molecule in cardiovascular disease with exercise.Cell stress & chaperones · 2026Review
- Plasma HMGB1 as a Potential Biomarker Reflecting the Clinical Outcome in Chronic Heart Failure Patients.Journal of clinical medicine · 2026Article
- RAGE signaling in acute myocardial infarction: sRAGE as a dynamic biomarker and emerging therapeutic target.Frontiers in endocrinology · 2026Review
- Screening and Targeting the HMGB1/RAGE Axis via Proteomics to Alleviate Inflammatory Responses in aJournal of inflammation research · 2026Article
- AGE-RAGE Axis and Cardiovascular Diseases: Pathophysiologic Mechanisms and Prospects for Clinical Applications.Cardiovascular drugs and therapy · 2025Review
- Acute binge alcohol increases risk of arrhythmias and myocardial fibrosis in a mouse model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Article
- Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology.International journal of molecular sciences · 2025Article
- Safety and toxicity risks of radiotherapy combined with PD-1/PD-L1 inhibitors: A comprehensive review.iScience · 2025Review
- Cardiovascular dysfunction and altered lysosomal signaling in a murine model of acid sphingomyelinase deficiency.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Virus and cell specific HMGB1 secretion and subepithelial infiltrate formation in adenovirus keratitis.PLoS pathogens · 2025Article
- KGF-2 Alleviates Dry Eye Disease by Regulating the HMGB1/TLR4 Pathway.Investigative ophthalmology & visual science · 2025Article
- The alarmin tandem: unraveling the complex effect of S100A8/A9 - from atherosclerosis to cardiac arrhythmias.Frontiers in immunology · 2025Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune response to cardiac troponin I (TnI) induces inflammation and fibrosis in the myocardium. High-mobility group box 1 (HMGB1) is a multifunctional protein that exerts proinflammatory activity by mainly binding to receptor for advanced glycation end products (RAGE). The involvement of the HMGB1-RAGE axis in the pathogenesis of inflammatory cardiomyopathy is yet not fully understood. Using the well-established model of TnI-induced experimental autoimmune myocarditis (EAM), we demonstrated that both local and systemic HMGB1 protein expression was elevated in wild-type (wt) mice after TnI immunization. Additionally, pharmacological inhibition of HMGB1 using glycyrrhizin or anti-HMGB1 antibody reduced inflammation in hearts of TnI-immunized wt mice. Furthermore, RAGE knockout (RAGE-ko) mice immunized with TnI showed no structural or physiological signs of cardiac impairment. Moreover, cardiac overexpression of HMGB1 using adeno-associated virus (AAV) vectors induced inflammation in the hearts of both wt and RAGE-ko mice. Finally, patients with myocarditis displayed increased local and systemic HMGB1 and soluble RAGE (sRAGE) expression. Together, our study highlights that HMGB1 and its main receptor, RAGE, appear to be crucial factors in the pathogenesis of TnI-induced EAM, because inhibition of HMGB1 and ablation of RAGE suppressed inflammation in the heart. Moreover, the proinflammatory effect of HMGB1 is not necessarily dependent on RAGE only. Other receptors of HMGB1 such as Toll-like receptors (TLRs) may also be involved in disease pathogenesis. These findings could be confirmed by the clinical relevance of HMGB1 and sRAGE. Therefore, blockage of one of these molecules might represent a novel therapeutic strategy in the treatment of autoimmune myocarditis and inflammatory cardiomyopathy.
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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.