Abstract 14395: Transcriptomes of Thrombi Retrieved by Mechanical Thrombectomy Can Distinguish Ischemic Stroke Subtypes

Abstract

Introduction: Determination of stroke etiology is crucial for prevention of secondary ischemic events. Diagnostic workups are intensive and expensive, and in cryptogenic cases are fruitless. Hypothesis: We hypothesize that thrombi from strokes of different etiologies have unique transcriptomic profiles. Methods: In 76 patients undergoing mechanical thrombectomy, we collect retrieved thrombi and extracted RNA on the PerkinElmer Chemagic 360. 48 samples of sufficient quality underwent 100-cycle, paired-end RNAseq on the Illumina NovaSeq6000. Transcriptomes with < 10M assigned reads were excluded; counts were normalized by transcripts per million. Significant differentially expressed genes (DEGs) between stroke subtypes (defined by Trial of Org 10172 in Acute Stroke Treatment) were identified by a false discovery rate-corrected F-test (q-value)<0.05 and an absolute fold-change>2. Bioinformatics and gene ontology enrichment analyses were performed to understand the pathobiology of DEGs. Results: We analyzed transcriptomes from 38 thrombi; 6 large artery atherosclerosis (LAA), 20 cardioembolism (CE), 5 other vasculopathy (OV), and 7 cryptogenic. Comparing CE to LAA, we found 218 DEGs that were related to greater Immune System Processes, Coagulation, and Regulation of Macrophage Activation. OV vs. LAA showed 414 DEGs, which reflected increased Regulation of Wound Healing, Biological Adhesion, and Cell Migration. Comparing CE to OV revealed 341 DEGs that were related to increased Cell Activation and Leukocyte Activation. Principal component analysis showed separation between these subtypes and that cryptogenic samples may be related to CE or OV. Conclusion: Transcriptomes of stroke thrombi can delineate etiology. CE thrombi are more inflammatory, while OV thrombi reflect wound healing responses. Cryptogenic thrombi may be related to multiple etiologies.