Role of Eosinophils in Spontaneous Coronary Artery Disease Pathogenesis

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

Spontaneous coronary artery dissection (SCAD) is a type of myocardial infarction (MI) predominantly affecting young women who have few risk factors for coronary artery disease. SCAD accounts for 25-30% of MI in women under 50 years of age and 15-20% of MI during pregnancy or during the peripartum period. SCAD can be fatal, and recurrence occurs in 10-20% of survivors of an initial episode. The underlying mechanism appears to be vascular fragility leading to dissection of the arterial wall and formation of an intramural hematoma that occludes the vessel lumen. Although patients presenting with SCAD do not have peripheral eosinophilia, postmortem histopathologic assessment of coronary artery tissue from SCAD patients has been reported to show an inflammatory infiltrate with frequent eosinophils. The aim of the present study was to confirm the presence of coronary artery eosinophilia as a recurrent feature in SCAD and to begin to explore the potential role of eosinophils in this rare condition. Postmortem specimens were obtained from the Office of the Suffolk County Medical Examiner through a public access request. Unstained sections from coronary arteries were evaluated by standard hematoxylin and eosin (H&E) staining, immunohistochemical staining for eosinophil peroxidase (EPX), and RNA in situ hybridization (RNA-ISH) to detect IL5 mRNA. Coronary artery specimens from 9 patients (8 female and 1 male; median age 47) who died following SCAD were evaluated. Although only three of the specimens showed an eosinophilic infiltrate after standard H&E staining, 7 showed staining for EPX, a marker of eosinophil activation in the tissue. Focal expression of interleukin 5 and eotaxin mRNA was observed in cells near the eosinophilic infiltrate in the same specimens consistent with recruitment of activated eosinophils to the area. Whether the recruited eosinophils contribute to disease pathogenesis or participate in tissue repair remains unknown but has important implications for potential therapeutic interventions.