Hypereosinophilia causes progressive cardiac pathologies in mice
Summary: 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 developm...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223020679 |
| _version_ | 1797647806691803136 |
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| author | Nicola Laura Diny Megan Kay Wood Taejoon Won Monica Vladut Talor Clarisse Lukban Djahida Bedja Nadan Wang Hannah Kalinoski Abdel Daoud C. Conover Talbot, Jr. Brian Leei Lin Daniela Čiháková |
| author_facet | Nicola Laura Diny Megan Kay Wood Taejoon Won Monica Vladut Talor Clarisse Lukban Djahida Bedja Nadan Wang Hannah Kalinoski Abdel Daoud C. Conover Talbot, Jr. Brian Leei Lin Daniela Čiháková |
| author_sort | Nicola Laura Diny |
| collection | DOAJ |
| description | Summary: 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 wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice. |
| first_indexed | 2024-03-11T15:21:48Z |
| format | Article |
| id | doaj.art-30640f6bca3044d2b937414794d30d52 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:21:48Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-30640f6bca3044d2b937414794d30d522023-10-28T05:09:14ZengElsevieriScience2589-00422023-10-012610107990Hypereosinophilia causes progressive cardiac pathologies in miceNicola Laura Diny0Megan Kay Wood1Taejoon Won2Monica Vladut Talor3Clarisse Lukban4Djahida Bedja5Nadan Wang6Hannah Kalinoski7Abdel Daoud8C. Conover Talbot, Jr.9Brian Leei Lin10Daniela Čiháková11W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Corresponding authorW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAInstitute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding authorSummary: 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 wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.http://www.sciencedirect.com/science/article/pii/S2589004223020679PhysiologyMolecular biologyCell biology |
| spellingShingle | Nicola Laura Diny Megan Kay Wood Taejoon Won Monica Vladut Talor Clarisse Lukban Djahida Bedja Nadan Wang Hannah Kalinoski Abdel Daoud C. Conover Talbot, Jr. Brian Leei Lin Daniela Čiháková Hypereosinophilia causes progressive cardiac pathologies in mice iScience Physiology Molecular biology Cell biology |
| title | Hypereosinophilia causes progressive cardiac pathologies in mice |
| title_full | Hypereosinophilia causes progressive cardiac pathologies in mice |
| title_fullStr | Hypereosinophilia causes progressive cardiac pathologies in mice |
| title_full_unstemmed | Hypereosinophilia causes progressive cardiac pathologies in mice |
| title_short | Hypereosinophilia causes progressive cardiac pathologies in mice |
| title_sort | hypereosinophilia causes progressive cardiac pathologies in mice |
| topic | Physiology Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223020679 |
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