Deciphering the Role of Immune cells in Thrombi of Acute Stroke Patients: A Novel Approach Through Spatial Transcriptomics

Abstract

Cardioembolic (CE) and large artery atherosclerosis (LAA) strokes are major causes of acute ischemic stroke (AIS), with a high recurrence risk. Studies on thrombus composition in AIS subtypes have yielded conflicting results, underscoring the need for further investigation. Immune cells such as neutrophils and macrophages promote thrombosis in cardiovascular diseases, but their role in thrombosis across AIS subtypes remains unclear. Here, we employed spatial transcriptomics to investigate the molecular characteristics of immune cells within thrombi from AIS patients with LAA and CE. Molecular profiling revealed distinct immune activities despite no significant differences in immune cell presence by immunostaining. LAA thrombi exhibited a profibrotic profile with CD163⁺ macrophages and upregulated TGF-β signaling. CE thrombi showed increased neutrophil activation and NET formation, with elevated CXCR4 expression. These findings suggest that targeting differential immune cell activation could provide etiology-specific therapeutic strategies to reduce recurrence and improve outcomes.