NF-κB aggravates cardiac vascular endothelial injury by sustained activation of the NLRP3 inflammasome after ischemic stroke in rats.

INTRODUCTION: Ischemic stroke elevates the risk of recurrent vascular events via endothelial cell activation-driven systemic inflammation, yet the existence and mechanisms of stroke-induced sustained pro-inflammatory changes in cardiac vascular endothelial cells remain unclear. METHODS: The male rat distal middle cerebral artery occlusion (dMCAO) model was established. The NF-κB/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. RESULTS: Ischemic stroke induced persistent cardiac vascular endothelial cell activation and upregulated VCAM-1/ICAM-1, which was mediated by NF-κB/NLRP3 signaling activation. Inhibiting this pathway or knocking down endothelial NF-κB effectively attenuated pro-inflammatory responses in cardiac vascular endothelial cells and reduced leukocyte infiltration after stroke. DISCUSSION: Our findings reveal a systemic mechanism for Stroke-Heart Syndrome, where ischemic stroke triggers persistent pro-inflammatory activation of cardiac vascular endothelial cells via the NF-κB/NLRP3 axis. This identifies the NF-κB/NLRP3-VCAM1/ICAM-1 pathway as a potential therapeutic target for preventing recurrent cardiac vascular events post-ischemic stroke.