Dataset Information

Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury.

ABSTRACT:

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

Reduced circulating Cav-1, with the potential to predict microembolic signals, was more frequently detected in recanalized stroke patients without early neurological improvement. At 24 h after tMCAO, serum Cav-1 was consistently reduced in mice. Endothelial Cav-1 was decreased in the peri-infarct region. Cav-1^-/- endothelium, with prominent barrier disruption, displayed extensive microthrombosis, accompanied by increased myeloid cell inflammatory infiltration after tMCAO. Specific enhanced expression of endothelial Cav-1 by AAV-Tie1-Cav-1 remarkably reduced infarct volume, attenuated vascular hyper-permeability and alleviated thrombo-inflammation in both wild-type and Cav-1^-/- 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC9508414 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury.

Zhang Xiaohao X Gong Pengyu P Zhao Ying Y Wan Ting T Yuan Kang K Xiong Yunyun Y Wu Min M Zha Mingming M Li Yunzi Y Jiang Teng T Liu Xinfeng X Ye Ruidong R Xie Yi Y Xu Gelin G

EBioMedicine 20220921

<h4>Background</h4>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.<h4>Methods</h4>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 v ...[more]

PMID: 36152520

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Dataset Information

Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury.

Background

Methods

Findings

Interpretation

Funding

Publications

Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury.

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