The NF-<i>κ</i>B/NLRP3 pathway and cardiac vascular endothelial cell activation were evaluated using proteomics analysis, immunohistochemistry, western blotting, quantitative real-time polymerase chain reaction, adeno-associated virus administration, and pharmacological interventions.<h4>Results</h4>Ischemic stroke induced persistent cardiac vascular endothelial cell activation and upregulated VCAM-1/ICAM-1, which was mediated by NF-<i>κ</i>B/NLRP3 signaling activation. Here, NLRP3 is linked to ischemic stroke.