Jiang Run-Hao, Liu Xing-Long, Xu Xiao-Quan, Shi Hai-Bin, Liu Sheng
Department of Interventional Radiology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People's Republic of China.
Department of Radiology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People's Republic of China.
Transl Stroke Res. 2024 Dec 18. doi: 10.1007/s12975-024-01317-x.
The objective of this study is to investigate the protein components of acute ischemic stroke (AIS) thrombi using four-dimensional independent data acquisition (4D-DIA) proteomics and reveal the correlations between thrombotic protein components and AIS etiology. From April to September 2023, we enrolled a total of 30 patients who underwent endovascular thrombectomy at our institute and were diagnosed in accordance with large artery atherosclerosis (LAA; n = 15) or cardioembolism (CE; n = 15). Thromboembolic material was collected for 4D-DIA proteomic detection. We then analyzed it for differentially expressed proteins (DEPs; fold change [FC] ≥ 1.5 or ≤ 0.67), performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and mapped protein-protein interactions (PPIs). In the 30 retrieved clots, 5115 proteins were expressed. Of these, we screened 246 DEPs between the LAA and CE groups, such as histone H4, collagen α1, and differentially expressed in neoplastic versus normal cells domain-containing protein 6A. GO analysis revealed that the DEPs' most important biological process was cellular process, the most important Cell Component was cell part, the molecular function was binding, and the most significantly enriched pathway was thiamine metabolism. PPI results revealed complicated interactions among these DEPs, of which superoxide dismutase, catalase, and γ-enolase might play important roles. This study outlines a promising molecular approach to differentiating the etiology of AIS between CE and LAA through the proteomics of retrieved thrombi, which might also inform future research into thrombotic biology.
本研究的目的是使用四维独立数据采集（4D-DIA）蛋白质组学研究急性缺血性卒中（AIS）血栓的蛋白质成分，并揭示血栓形成蛋白质成分与AIS病因之间的相关性。2023年4月至9月，我们共纳入了30例在我院接受血管内血栓切除术且根据大动脉粥样硬化（LAA；n = 15）或心源性栓塞（CE；n = 15）确诊的患者。收集血栓栓塞物质进行4D-DIA蛋白质组学检测。然后我们对其进行差异表达蛋白（DEP；变化倍数[FC]≥1.5或≤0.67）分析，进行基因本体论（GO）和京都基因与基因组百科全书通路富集分析，并绘制蛋白质-蛋白质相互作用（PPI）图谱。在检索到的30个凝块中，共表达了5115种蛋白质。其中，我们筛选出LAA组和CE组之间的246种DEP，如组蛋白H4、胶原蛋白α1和含肿瘤与正常细胞差异表达结构域蛋白6A。GO分析显示，DEP最重要的生物学过程是细胞过程，最重要的细胞成分是细胞部分，分子功能是结合，最显著富集的通路是硫胺素代谢。PPI结果揭示了这些DEP之间复杂的相互作用，其中超氧化物歧化酶、过氧化氢酶和γ-烯醇化酶可能起重要作用。本研究概述了一种有前景的分子方法，通过对回收血栓的蛋白质组学来区分CE和LAA之间AIS的病因，这也可能为未来血栓形成生物学的研究提供参考。
