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.

Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

“…Even more so, eosinophils are capable of presentation of antigens to Th2-lymphocytes and may even activate dendritic cells through the production of eosinophil peroxidase (EPO) ( 48 ). Eosinophils were also shown to be involved in the pathogenesis of myocardial infarction, reaching the peak in plasma by days 2-3 post-AMI ( 49 ). They may increase damage of myocardial tissue through the production of ROS by eosinophil peroxidase or induction of cellular cytotoxicity by granules’ contents or antibody-mediated cellular cytotoxicity ( 47 ).…”

“…Eosinophils also secrete IL-4, cytokine playing an essential role in differentiation of macrophages towards M2 phenotype, and regulating myocardial tissue regeneration ( 53 , 54 ). Eosinophilic cationic protein mEar1 together with IL-4 was able to inhibit apoptosis is cardiomyocytes and prevent adhesion of neutrophils to endothelial wall, improving cardiac dysfunction ( 49 ). Most likely production of IL-4 is a key feature providing beneficial effects of eosinophils during AMI, as injection of the recombinant IL-4 to eosinophil-deficient mice rescued adverse remodeling of the left ventricle after the permanent ligation of the left coronary artery ( 54 ).…”

“…There still remains many unresolved questions in the role of eosinophils in post-infarct inflammation, such as gender bias, as many aspects of homeostatic and anti-inflammatory activity of eosinophils have only been confirmed in males, and were not established in females yet ( 49 ).…”

Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases

“…Thus, under baseline conditions, eosinophils rapidly enter several tissues, mainly the gastrointestinal tract, adipose tissue, thymus, uterus, and mammary glands, where they promote a variety of essential homeostatic functions, such as immunoregulation, tissue repair, glucose homeostasis, protection against obesity, regulation of mammary gland development, and preparation of the uterus for pregnancy (reviewed in [ 1 ]). Moreover, eosinophils promote antitumor effects in colorectal cancer [ 2 , 3 , 4 ], hepatoprotective activities [ 5 ], and cardiac protection after myocardial infarction [ 6 ].…”

Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins

“…An important function of eosinophils is their antitumor effect in colorectal cancer [ 246 ]. Eosinophils show hepatoprotective activity [ 247 ] and cardiac protective function after myocardial infarction [ 248 ]. Of particular interest, a robust inverse correlation between eosinophil numbers and coronavirus disease 2019 (COVID-19) infection severity was observed most recently [ 249 ].…”