Hypereosinophilia causes progressive cardiac pathologies in mice
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
Affiliations
Nicola Laura Diny
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Corresponding author
Megan Kay Wood
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
Taejoon Won
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Monica Vladut Talor
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Clarisse Lukban
Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Djahida Bedja
Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Nadan Wang
Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hannah Kalinoski
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
Abdel Daoud
W. 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
C. Conover Talbot, Jr.
Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Brian Leei Lin
Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Daniela Čiháková
W. 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 author
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.
