Acute myocardial infarction is among the leading causes of death. Mechanisms of coronary plaque rupture are poorly understood. In contrast to common knowledge implicating monocytes and T-cells in the pathogenesis of acute coronary vascular syndromes, we hypothesize that circulating inflammatory cells mediate plaque rupture and thrombotic occlusion. The goal of this study was to phenotype inflammatory cells at the site of plaque rupture.Methods
Patients with acute coronary syndromes who underwent primary percutaneous coronary intervention at the Vienna General Hospital were consented (n=40). Culprit site blood was aspirated with a thrombectomy catheter and particulate thrombus material was separated. In parallel, blood was sampled from the femoral arterial sheath. Flow cytometry was employed to determine cell types accumulating at the plaque rupture site. These results were complemented by ELISA, cell culture and immunofluorescence assays.Results
The vast majority of inflammatory cells at the culprit lesion site are neutrophils. Coronary neutrophils overexpress CD66b, are apoptosis-resistant, and produce large amounts of neutrophil extracellular traps (DNA/histone complexes). Plaque-site monocytes display a CD14lowCD16high phenotype that is found in aggregation with platelets. CD4CD28null T-cells are increased with low content of Perforin and Granzyme B.Conclusion
The selective enrichment of innate inflammatory cell subsets at the culprit lesion site indicates a disease-specific inflammatory process, suggesting an outside-in mechanism of acute atherosclerotic vascular obstruction.