Author + information
- Received August 28, 2019
- Revision received May 12, 2020
- Accepted May 12, 2020
- Published online July 27, 2020.
- Iqbal S. Toor, MBChBa,
- Dominik Rückerl, PhDb,
- Iris Mair, PhDc,
- Rob Ainsworth, MBChBd,
- Marco Meloni, PhDa,
- Ana-Mishel Spiroski, PhDa,
- Cecile Benezech, PhDa,
- Jennifer M. Felton, PhDc,
- Adrian Thomson, BSca,
- Andrea Caporali, PhDa,
- Thomas Keeble, MDe,f,
- Kare H. Tang, MBChBe,
- Adriano G. Rossi, DScc,
- David E. Newby, DSca,
- Judith E. Allen, PhDb and
- Gillian A. Gray, PhDa,∗ ()
- aBritish Heart Foundation/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
- bFaculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
- cMRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
- dDivision of Pathology, Deanery of Molecular, Genetic and Population Sciences, University of Edinburgh, Edinburgh, United Kingdom
- eEssex Cardiothoracic Centre, Basildon and Thurrock Hospitals NHS Foundation Trust, Essex, United Kingdom
- fSchool of Medicine, Anglia Ruskin University, Cambridge, United Kingdom
- ↵∗Address for correspondence:
Dr. Gillian A. Gray, BHF/University Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
• A drop in eosinophil blood count is associated with recruitment of eosinophils to the heart during repair following clinical and experimental MI.
• Genetic and pharmacological eosinophil depletion leads to increased adverse remodeling in experimental MI.
• Eosinophils are required for acquisition of an anti-inflammatory macrophage phenotype, a shift to resolution of inflammation and mature scar formation during infarct repair.
• IL-4 therapy is able to rescue the adverse remodeling phenotype in conditions of eosinophil deficiency.
In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted in attenuated anti-inflammatory macrophage polarization, enhanced myocardial inflammation, increased scar size, and deterioration of myocardial structure and function. Adverse cardiac remodeling in the setting of eosinophil deficiency was prevented by interleukin-4 therapy.
The study was supported by British Heart Foundation Centre of Research Excellence funding. Dr. Toor is supported by a Wellcome Trust Edinburgh Clinical Academic Track fellowship (104799/Z/14/Z). Dr. Rossi is supported by a Medical Research Council-UK Programme Grant (MR/K013386/1). Dr. Allen is supported by a Medical Research Council-UK programme grant (MR/K01207X/1). Dr. Newby is supported by the British Heart Foundation (CH/09/002, RE/13/3/30183, RM/13/2/30158; RG/16/10/32375) and a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Rückerl is supported by a Medical Research Council-UK Project grant (MR/P02615X/1). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received August 28, 2019.
- Revision received May 12, 2020.
- Accepted May 12, 2020.
- 2020 The Authors