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BACKGROUND: Thrombo-inflammation is an important checkpoint that orchestrates infarct development in ischemic stroke. However, the underlying mechanism remains largely unknown. Here, we explored the role of endothelial Caveolin-1 (Cav-1) in cerebral thrombo-inflammation. METHODS: The correlation between serum Cav-1 level and clinical outcome was analyzed in acute ischemic stroke patients with successful recanalization. Genetic manipulations by endothelial-specific adeno-associated virus (AAV) and siRNA were applied to investigate the effects of Cav-1 in thrombo-inflammation in a transient middle cerebral artery occlusion (tMCAO) model. Thrombo-inflammation was analyzed by microthrombosis formation, myeloid cell infiltration, and endothelial expression of adhesion molecules as well as inflammatory factors. FINDINGS: tMCAO mice. Transcriptome analysis after tMCAO further designated Rxrg as the most significantly changed molecule resulting from the knockdown of Cav-1. Supplementation of RXR-γ siRNA reversed AAV-Tie1-Cav-1-induced amelioration of thrombo-inflammation without affecting endothelial tight junction. INTERPRETATION: Endothelial Cav-1/RXR-γ may regulate infarct volume and neurological impairment, possibly through selectively controlling thrombo-inflammation coupling, in cerebral ischemia/reperfusion. FUNDING: This work was supported by National Natural Science Foundation of China.
Zhang et al. (Wed,) studied this question.