Hypereosinophilia causes progressive cardiac pathologies in mice

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...

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Bibliographic Details
Published in:bioRxiv 2022-05
Main Authors: Diny, Nicola Laura, Wood, Megan K, Taejoon Won, Talor, Monica Vladut, Lukban, Clarisse, Bedja, Djahida, Wang, Nadan, Talbot, C Conover, Lin, Brian Leei, Cihakova, Daniela
Format: Article
Language:English
Subjects:
Cardiomyocytes
Eosinophilia
Gene expression
Inflammation
Interleukin 5
Leukocytes (eosinophilic)
Muscle contraction
Transgenic mice
Ventricle
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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 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.05.04.490445