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.