699 Immune Activation on Stroke Thrombus Proteome Associated With Failed First Pass Recanalization by Thrombectomy

Abstract

INTRODUCTION: Endovascular thrombectomy remains one of the most potent tools in the treatment kit for acute ischemic stroke. Prior cursory histopathological studies have demonstrated relationships between cellular composition of the thrombus and successful endovascular treatment. METHODS: Quantitative proteomes were generated using mass spectrometry from thromboembolic material from 59 stroke patients retrieved by mechanical thrombectomy. Clinical data, including whether or not Thrombolysis In Cerebral Infarction (TICI) score of 2b or greater was achieved on the first pass (FP±), was gathered by retrospective chart review. FP effect was related to the clinical variables, as well as the abundances of proteins identified by mass spectrometry. Finally, gene ontology and KEGG pathway analysis was used to examine the functional implications of proteins significantly associated with FP±. RESULTS: Both discharge and 90-day follow-up mRS were significantly greater in greater in patients who were FP- (Wilcoxon; Z = -1.84, -2.32; p = 0.03, 0.01). Additionally, mortality was significantly associated with FP effect (Fisher’s; p = 0.04). Numerous proteins were negatively and positively associated with FP± (Wilcoxon; 1.6 < |Z| < 2.8, p < 0.05). Notably, several neutrophil and histone proteins were associated with FP- thrombectomy (Wilcoxon; |Z| > 1.9, p < 0.05). GO tags represented in the proteins FP- thrombectomy included, among others, immune activation and granule secretion (padj < 0.001). KEGG pathways significantly represented in the FP- group also include immune activation, in particular neutrophil degranulation (padj < 1E-13). CONCLUSIONS: This study suggests that not only is angiographic FP effect significantly associated with short and long-term functional outcomes, but it is also associated with significant proteome-level differences in the composition of retrieved stroke thrombi. Specifically, immune activation may be related to failure to achieve FP recanalization.