Abstract 14113: Atrial Fibrillation Associated With Differences in Proteomic Composition of Retrieved Acute Ischemic Stroke Emboli

Abstract

Introduction: Study of the composition of acute ischemic stroke emboli is still in infancy, though recent literature has begun to demonstrate remarkable heterogeneity in the composition of ischemic stroke emboli from different etiologies. Atrial fibrillation (AF) is a significant risk factor for stroke, and so in this study we investigate differences in proteomic composition between retrieved stroke emboli from patients with and without AF. Methods: The full proteomic composition of retrieved thromboembolic material from 24 patients with AIS was evaluated by mass spectrometry. The abundance of individual proteins in patients with AF was compared to that of patients without AF using Mann-Whitney U-tests, with significant differences described by the fold change (FC) in abundance. Cut-offs for significance were set at p = 0.05 and an FC difference of 2x. Descriptive heatmaps with sorted dendrograms were generated using the proteins with significant FC differences between patients with and without AF. Results: Proteins with the greatest FC enrichment in emboli from patients with AF included ferritin light chain (p = 0.006), ferritin heavy chain (p = 0.003), eosinophil peroxidase (p = 0.01), eosinophil lysophospholipase (p = 0.02), eosinophil-derived neurotoxin (p = 0.02), the neprilysin modulator nicastrin (p = 0.0007), HLA class I B α chain (p = 0.02), among others. Notably, neutrophil and histone proteins were also significantly enriched in emboli from patients with AF (p < 0.05 for all). Proteins with the greatest FC enrichment in emboli from patients without AF included interferon-induced GTP-binding protein Mx1 (p78) (p = 0.04) and mitsugumin-53 (p = 0.03). Conclusions: This data demonstrates that clot composition may directly reflect underlying stroke etiology. More specifically, the enrichment of eosinophil, neutrophil, and histone proteins in emboli from patients with AF points to significant immunothrombosis in emboli from this patient population. These findings may underlie distinct mechanisms in clot formation or maintenance in AF, and inform not only future studies on stroke pathophysiology, but also future work on novel pharmacotherapies for acute ischemic stroke in this patient population.