Eosinophils improve cardiac function after myocardial infarction

Jing Liu; Chongzhe Yang; Tianxiao Liu; Zhiyong Deng; Wenqian Fang; Xian Zhang; Jie Li; Qin Huang; Conglin Liu; Yunzhe Wang; Dafeng Yang; Galina K. Sukhova; Jes S. Lindholt; Axel Diederichsen; Lars M. Rasmussen; Dazhu Li; Gail Newton; Francis W. Luscinskas; Lijun Liu; Peter Libby; Jing Wang; Junli Guo; Guo Ping Shi

doi:10.1038/s41467-020-19297-5

Eosinophils improve cardiac function after myocardial infarction

Jing Liu, Chongzhe Yang, Tianxiao Liu, Zhiyong Deng, Wenqian Fang, Xian Zhang, Jie Li, Qin Huang, Conglin Liu, Yunzhe Wang, Dafeng Yang, Galina K. Sukhova, Jes S. Lindholt, Axel Diederichsen, Lars M. Rasmussen, Dazhu Li, Gail Newton, Francis W. Luscinskas, Lijun Liu, Peter LibbyJing Wang, Junli Guo^*, Guo Ping Shi

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H₂O₂- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.

Original language	English
Article number	6396
Journal	Nature Communications
Volume	11
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-020-19297-5
Publication status	Published - 16. Dec 2020

Keywords

Aged
Animals
Cell Death
Diphtheria Toxin/toxicity
Electrocardiography
Eosinophils/drug effects
Female
Fibroblasts/pathology
Humans
Interleukin-4/genetics
Male
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Myocardial Infarction/physiopathology
Myocardium/pathology
Myocytes, Cardiac/pathology
Ribonucleases/genetics

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10.1038/s41467-020-19297-5Licence: CC BY

Open Access VersionFinal published version, 11 MBLicence: CC BY

Cite this

Liu, J., Yang, C., Liu, T., Deng, Z., Fang, W., Zhang, X., Li, J., Huang, Q., Liu, C., Wang, Y., Yang, D., Sukhova, G. K., Lindholt, J. S., Diederichsen, A., Rasmussen, L. M., Li, D., Newton, G., Luscinskas, F. W., Liu, L., ... Shi, G. P. (2020). Eosinophils improve cardiac function after myocardial infarction. Nature Communications, 11, Article 6396. https://doi.org/10.1038/s41467-020-19297-5

@article{bfeed20033a84f7eb85a24ce8f51dea6,

title = "Eosinophils improve cardiac function after myocardial infarction",

abstract = "Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.",

keywords = "Aged, Animals, Cell Death, Diphtheria Toxin/toxicity, Electrocardiography, Eosinophils/drug effects, Female, Fibroblasts/pathology, Humans, Interleukin-4/genetics, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Myocardial Infarction/physiopathology, Myocardium/pathology, Myocytes, Cardiac/pathology, Ribonucleases/genetics",

author = "Jing Liu and Chongzhe Yang and Tianxiao Liu and Zhiyong Deng and Wenqian Fang and Xian Zhang and Jie Li and Qin Huang and Conglin Liu and Yunzhe Wang and Dafeng Yang and Sukhova, {Galina K.} and Lindholt, {Jes S.} and Axel Diederichsen and Rasmussen, {Lars M.} and Dazhu Li and Gail Newton and Luscinskas, {Francis W.} and Lijun Liu and Peter Libby and Jing Wang and Junli Guo and Shi, {Guo Ping}",

year = "2020",

month = dec,

day = "16",

doi = "10.1038/s41467-020-19297-5",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Liu, J, Yang, C, Liu, T, Deng, Z, Fang, W, Zhang, X, Li, J, Huang, Q, Liu, C, Wang, Y, Yang, D, Sukhova, GK, Lindholt, JS , Diederichsen, A , Rasmussen, LM, Li, D, Newton, G, Luscinskas, FW, Liu, L, Libby, P, Wang, J, Guo, J & Shi, GP 2020, 'Eosinophils improve cardiac function after myocardial infarction', Nature Communications, vol. 11, 6396. https://doi.org/10.1038/s41467-020-19297-5

TY - JOUR

T1 - Eosinophils improve cardiac function after myocardial infarction

AU - Liu, Jing

AU - Yang, Chongzhe

AU - Liu, Tianxiao

AU - Deng, Zhiyong

AU - Fang, Wenqian

AU - Zhang, Xian

AU - Li, Jie

AU - Huang, Qin

AU - Liu, Conglin

AU - Wang, Yunzhe

AU - Yang, Dafeng

AU - Sukhova, Galina K.

AU - Lindholt, Jes S.

AU - Diederichsen, Axel

AU - Rasmussen, Lars M.

AU - Li, Dazhu

AU - Newton, Gail

AU - Luscinskas, Francis W.

AU - Liu, Lijun

AU - Libby, Peter

AU - Wang, Jing

AU - Guo, Junli

AU - Shi, Guo Ping

PY - 2020/12/16

Y1 - 2020/12/16

N2 - Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.

AB - Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.

KW - Aged

KW - Animals

KW - Cell Death

KW - Diphtheria Toxin/toxicity

KW - Electrocardiography

KW - Eosinophils/drug effects

KW - Female

KW - Fibroblasts/pathology

KW - Humans

KW - Interleukin-4/genetics

KW - Male

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Myocardial Infarction/physiopathology

KW - Myocardium/pathology

KW - Myocytes, Cardiac/pathology

KW - Ribonucleases/genetics

U2 - 10.1038/s41467-020-19297-5

DO - 10.1038/s41467-020-19297-5

M3 - Journal article

C2 - 33328477

AN - SCOPUS:85097628912

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 6396

ER -

Eosinophils improve cardiac function after myocardial infarction

Abstract

Keywords

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