Background Low peripheral blood eosinophil count is associated with increased risk of mortality in ischaemic heart disease patients. Eosinophils contain preformed IL-4 within their cytoplasmic granules, which promotes an anti-inflammatory response and is associated with tissue repair. Whether eosinophils are recruited to the infarct zone and have a role in regulating infarct repair is currently unknown.
Purpose This study sought to investigate the role of eosinophils in infarct healing.
Methods MI was induced by permanent coronary artery ligation in 12–15 week-old male wild-type (WT) BALB/c and eosinophil deficient ΔdblGATA mice. Cardiac function was assessed 7 days later by high-resolution ultrasound. A cohort of 732 patients undergoing emergency percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) were followed up for 6 month all-cause mortality.
Results Histochemical staining (Siglec F+) and single cell digestion of infarcted WT BALB/c hearts revealed significant recruitment of (CD11b+SiglecF+Ly6Gint) eosinophils to the infarcted heart. Genetic eosinophil deficiency in ΔdblGATA mice led to greater left ventricular dilatation relative to WT BALB/c mice and worse cardiac function at Day 7 post-MI. Patients with a low eosinophil count at Day 1 following STEMI had an increased risk of 6 month all-cause mortality. On multivariate analysis the hazard ratio of all-cause mortality in the first tertile of peripheral blood eosinophil count at Day 1 post-MI was 6.97 [2.18–22.32] compared to the highest tertile (p=0.001). Treatment with IL-4 complexes was able to rescue the adverse cardiac remodelling of eosinophil-deficient ΔdblGATA mice. Expression of plod2, lox and Fmod genes, which are involved in post-translational collagen modification, were increased in hearts from ΔdblGATA mice. This was accompanied with longer infarct length in ΔdblGATA mice compared to WT BALB/c mice (p=0.01).
Conclusions This study provides the first evidence for an essential role of eosinophils in the tissue repair response following MI, through regulating genes associated with connective tissue biogenesis. Patients with a low eosinophil post-MI may benefit from IL-4 therapy to improve outcome.
- myocardial infarction
- cardiac remodelling
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