Stroke emboli from patients with atrial fibrillation enriched with neutrophil extracellular traps.

ABSTRACT

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy. Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively). Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry. Known marker proteins were assigned groups representing broad classes of embolus components red blood cells, platelets, neutrophils, eosinophils, histones, complement, and other clotting-associated proteins (eg, fibrinogen). Relative protein abundances were compared between AF+ and AF- samples. Functional implications of differences were explored with gene set enrichment analysis and Gene Ontology enrichment analysis and visualization tool. Results: One hundred sixty-six proteins were differentially expressed between AF+ and AF- specimens. Eight out of the 15 neutrophil proteins (P < .05; fold change, >2) and 4 of the 14 histone proteins were significantly enriched in AF+ emboli (P < .05; fold change, >2). Gene set enrichment analysis revealed a significant representation of proteins from published neutrophil extracellular trap (NET) proteomic gene sets. The most significantly represented functional Gene Ontology pathways in patients with AF involved neutrophil activation and degranulation (P < 1 × 10-7). Conclusion: The present analysis suggests enrichment of NETs in emboli of patients with stroke and AF. NETs are a significant though understudied structural component of thrombi. This work suggests not only unique stroke biology in AF but also potential therapeutic targets for AIS in this population.