急性心肌梗死患者冠脉内微粒促进血管生成及其机制研究

Key function of Microparticles(MP) in cardiovascular disease raises widely concern in recent years. It has been proved to participate in many important pathological processes including thrombosis, inflammation and angiogenesis. By collecting blood samples from patients treated with thrombus aspiration, MP from infarct related coronary artery can be isolated and purified. Our pilot experiments indicated that compared with MPs from circulating blood, the MPs from coronary can upregulate endothelium and smooth muscle cell migration ability, and promote angiogenesis. Our pilot experiments tried to offer an ex-vivo explaination of angiogenesis after myocardial infarction. The difference of MPs generated from circulating blood and aspirated blood in infarct artery will be detected by flow-cytometry, and of noted, an effect to PI3K/AKT/eNOS signal pathway in endothelium and P38 signal pathways, which are closely connected with migration and angiogenesis, are observed being upregulated by coronary MP compared with circulating MP. Proteomics and lipidomics analysis methods will be carried out to elucidate the difference existing between coronary MP and circulating MP, as well as bioinformatics analysis technique that will deal with further pathological explanation. Hopefully, it will provide a better illustration for mechanism responsible for endothelial and smooth muscle cell migration and angiogenesis ability after myocardial infarction.

微粒（Microparticles, MP）广泛参与了凝血、炎症、血管生成等心血管疾病相关的病理生理过程，然而对于其在急性冠脉综合征发病后血管生成过程中的功能，尚无直接研究。我们对采取血栓抽吸术的急诊心梗患者，留取梗死相关冠脉局部血液，分离提取冠脉内血浆微粒，发现与外周MP相比,冠脉MP可以明显提高内皮、平滑肌细胞的迁移能力。第一次证明了心梗后冠脉血管内MP具有更强的促血管生成能力，为心梗后血管新生提出了新的更有力的解释。为分析其具体机制，我们用流式细胞仪比较了冠脉MP与外周血MP的数量、种类差异，发现冠脉内MP含量明显较外周血液高。我们通过预实验还发现冠脉MP能够上调内皮细胞迁移、血管生成相关的PI3K/AKT/eNOS通路、平滑肌细胞的P38通路。我们希望进一步探索冠脉MP促进血管生成的相关机理，并通过蛋白质组学和脂质组学分析寻找抽吸MPs与外周MPs的差异，探索其具体分子机制。

微粒（Microparticles，MPs）是介导病理生理过程的重要信使。然而对于其在急性冠脉综合征发病后血管生成过程中的作用，尚无直接研究。本研究主要探讨梗死相关动脉内MPs是否具有促血管新生的作用，并进一步研究其发挥作用的机制。收集行急诊PCI并血栓抽吸的ST段抬高心肌梗死（STEMI）患者梗死相关动脉血栓抽吸处及穿刺处主动脉循环血液分离提取MPs，发现STEMI患者梗死相关动脉处血中MPs含量比主动脉循环血中MPs要多；梗死相关动脉处血中MPs不引起内皮细胞增殖，可以促进内皮细胞迁移和小管形成，通过激活PI3K/AKT/eNOS/VEGF 信号通路发挥作用；梗死相关动脉处血中MPs不引起内皮舒张功能紊乱且具有提高大鼠急性心梗后心功能，减少心肌纤维化的作用。STEMI患者梗死相关动脉处血中MPs为心肌梗死后血管生成及侧支循环的构建提供了新的解释，为STEMI的治疗提供了新的治疗思路和靶点，具有潜在的应用价值。