RT Journal Article
SR Electronic
T1 Hypereosinophilia causes progressive cardiac pathologies in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.04.490445
DO 10.1101/2022.05.04.490445
A1 Nicola Laura Diny
A1 Megan Kay Wood
A1 Taejoon Won
A1 Monica Vladut Talor
A1 Clarisse Lukban
A1 Djahida Bedja
A1 Nadan Wang
A1 C. Conover Talbot, Jr.
A1 Brian Leei Lin
A1 Daniela Čiháková
YR 2022
UL http://biorxiv.org/content/early/2022/05/05/2022.05.04.490445.abstract
AB 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.Teaser Too many eosinophils cause inflammation in the heart and change cardiomyocyte contraction leading to poor heart function.Competing Interest StatementThe authors have declared no competing interest.