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

doi:10.1016/j.isci.2023.107990

Hypereosinophilia causes progressive cardiac pathologies in mice

iScience. 2023 Sep 21;26(10):107990. doi: 10.1016/j.isci.2023.107990. eCollection 2023 Oct 20.

Authors

Affiliations

¹ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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 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.

Keywords: Cell biology; Molecular biology; Physiology.

Abstract

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