Hypereosinophilia causes progressive cardiac pathologies in mice
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Abstract
Abstract Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to WT controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca 2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice. Teaser Too many eosinophils cause inflammation in the heart and change cardiomyocyte contraction leading to poor heart function.
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IL-5 transgenic mice with hypereosinophilia spontaneously develop eosinophilic myocarditis at a low incidence.
“IL-5 transgenic mice with hypereosinophilia spontaneously developed eosinophilic myocarditis at a low incidence”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [80]
The Introduction and Results describe spontaneous cardiac disease and predominantly eosinophilic heart infiltration in hypereosinophilic IL-5Tg mice. However, the paper does not report a low incidence of spontaneous eosinophilic myocarditis; the Discussion distinguishes this progressive disease from experimentally induced myocarditis. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIL-5 transgenic mice with hypereosinophilia develop significant cardiac dysfunction as they age.
“along with significant cardiac dysfunction as they aged.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [80]
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Diny, N. L., Yamada, Y., & Zimmermann, N. (2025) · Frontiers in Allergy · doi:10.3389/falgy.2025.1740057 · Cited by 2 · see citing works
Self-citationCongestive heart failure secondary to hypereosinophilic syndrome with cardiac involvement in a cat
Gomez, P., Ward, J. L., Manson, E., & Fasina, O. O. (2026) · Journal of Veterinary Cardiology · doi:10.1016/j.jvc.2026.05.004
- Authors
- Diny, N. L., Wood, M. K., Won, T., Talor, M. V., Lukban, C., Bedja, D., Wang, N., Kalinoski, H., Daoud, A., Talbot, C. C., Leei Lin, B., & Čiháková, D.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Diny, Nicola Laura
- Čiháková, Daniela
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 26
- Issue
- 10
- Pages
- 107990
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC10565781
- OpenAlex
- W4386879935
- Cited by
- 7
- References
- 79
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association (15PRE25400010, 19TPA34910007, 20TPA35490421, 23EIA1040103)
- National Institutes of Health (R01HL118183, R01HL136586)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (F31AR077406)
- Topics
- Health Sciences › Medicine › Rheumatology › Eosinophilic Disorders and Syndromes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- hypereosinophilia, eosinophilic cardiomyopathy, cardiac pathology, eosinophils, mouse model
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