靶向NETs超声分子成像预测动脉粥样硬化血栓形成

早期、特异性识别具有血栓形成风险的动脉粥样硬化高危斑块是临床急需、影像学研究的热点。近期研究显示中性粒细胞胞外诱捕网（NETs）启动和促进动脉粥样硬化斑块血栓形成，我们前期在ApoE-/-小鼠动脉粥样硬化血栓模型中发现：NETs表达先于动脉粥样硬化血栓形成，且与血栓形成存在极强的相关性，提示NETs表达增加可以预测急性血栓事件。因此我们假设：靶向NETs超声分子成像可以早期、在体、定位、定量预测动脉粥样硬化急性血栓事件。本项目拟通过构建靶向NETs的超声微泡，利用超声分子成像，通过多时间点动态观察超声信号与血栓形成的关系，A.探究NETs表达变化与血栓形成的相关性；B.验证NETs作为预测急性血栓事件早期特异性靶点的可行性；C.实现早期可视化动态预测动脉粥样硬化急性血栓事件。本项目实施将有利于为临床提供早期特异性预测高危斑块的新靶点，实现早期预警和及时干预急性血栓事件这一重大目标。

Early and specific identification of high-risk atherosclerotic plaques responsible for acute thrombotic events is a hot issue in clinical and imaging research. Recent studies have shown that neutrophil extracellular traps (NETs) formation could initiate and promote atherothrombosis. In our previous experiments, we have established a atherothrombotic model in apolipoprotein E-deficient (ApoE-/-) mice. Our results have shown that NETs were preceded and in strongly positive relationship with atherothrombosis, which suggested that increased expression of NETs could predict acute thrombotic events of atherosclerosis. Therefore, we hypothesized that targeting NETs by ultrasound molecular imaging could achieve early, positionable and quantitative prediction of acute atherothrombotic events in vivo. This project is proposed to dynamically observe the relationship between ultrasound signal and atherothrombosis through multiple time points by constructing NETs specific targeting microbubbles and using ultrasound molecular imaging. We sought to (1) explore the correlation between NETs expression and atherosclerotic thrombosis;(2) demonstrate the feasibility of NETs as an early and specific target for the prediction of acute thrombotic events; (3) achieve early, visualized and dynamic prediction of acute atherothrombotic events. The aim of this study is to provide a new target for early and specific prediction of high-risk plaques, enabling early warning and timely intervention of acute thrombotic events.