| Literature DB >> 33328477 |
Jing Liu1,2, Chongzhe Yang1, Tianxiao Liu1,2, Zhiyong Deng1, Wenqian Fang1, Xian Zhang1, Jie Li1, Qin Huang1, Conglin Liu1, Yunzhe Wang1, Dafeng Yang1, Galina K Sukhova1, Jes S Lindholt3,4,5, Axel Diederichsen4,6, Lars M Rasmussen4,7, Dazhu Li2, Gail Newton8, Francis W Luscinskas8, Lijun Liu9, Peter Libby1, Jing Wang10, Junli Guo11,12, Guo-Ping Shi13.
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.Entities:
Year: 2020 PMID： 33328477 DOI： 10.1038/s41467-020-19297-5
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919