Eosinophils improve cardiac function after myocardial infarction

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.

Note that full information on the approval of the study protocol must also be provided in the manuscript.
We used C57BL/6 (000664) and Balb/c (000651) wild type mice purchased from the Jackson laboratory. No wild animals and no field collected samples were used in the study.
We collected mouse heart to test the heart immune cells in different time points post-MI, such as post-MI day 1, 3, 5, and 7. We collected mouse heart for immunostainning one-month post-MI. We also collected spleen for immune cell analysis. We collected liver, kidney, plasma for potential use. No field collected samples were used in the study.
All animal procedures conformed to the guide for the Care and Use of Laboratory Animal published by the US National Instituted of Health and was approved by the Brigham and Women's Hospital Standing Committee on Animals (protocol #2016N000442) The DANCAVAS trial is a population-based, randomized, and clinically-controlled screening trial of men aged 65-74. No exclusion criteria were used. One-third was invited for cardiovascular screening examinations including a CT scan at one of the four locations, among which 62.4% men attended. The screening includes a low-dose, noncontrast computerized tomography scan to detect coronary artery calcification and aortic and iliac aneurysms; brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension; a telemetric assessment of heart rhythm; and a measurement of blood cholesterol and glucose levels. For the purpose of this study, leucocyte count, including EOS, was also performed. At attendance of screening, each man was first given the informed consent, then a medical history was obtained including previous acute myocardial infarction (AMI), coronary revascularization, chronic obstructive pulmonary disease (COPD), medication history, and symptoms. In case of dyspnoea, NYHA classification was performed. Up-to-date cardiovascular preventive treatment was recommended in case of subclinical cardiovascular disease. Use of decoded patient information was pre-proved by the Human Investigation Review Committee at the Brigham and Women's Hospital, Boston, MA, USA (protocol #2010P001930). No patient informed consent was required.
Human blood was from healthy donor in Massachusetts General Hospital.
The human population included men attending the Danish Cardiovascular Screening Trial (DANCAVAS) in Odense. We consecutively selected 5,864 men who had blood EOS counts available. The DANCAVAS trial is a population-based, randomized, and clinically-controlled screening trial of men aged 65-74. No exclusion criteria were used. One-third was invited for cardiovascular screening examinations including a CT scan at one of the four locations, among which 62.4% men attended. The screening includes a low-dose, noncontrast computerized tomography scan to detect coronary artery calcification and aortic and iliac aneurysms; brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension; a telemetric assessment of heart rhythm; and a measurement of blood cholesterol and glucose levels. For the purpose of this study, leucocyte count, including EOS, was also performed. At attendance of screening, each man was first given the informed consent, then a medical history was obtained including previous acute myocardial infarction (AMI), coronary revascularization, chronic obstructive pulmonary disease (COPD), medication history, and symptoms. In case of dyspnoea, NYHA classification was performed. Up-to-date cardiovascular preventive treatment was recommended in case of subclinical cardiovascular disease.
Use of decoded patient information was pre-proved by the Human Investigation Review Committee at the Brigham and Women's Hospital, Boston, MA, USA (protocol #2010P001930). No patient informed consent was required.