Li Yanfei, Wang Cuiping, Li Tingting, Ma Linlin, Fan Fangzhou, Jin Yueling, Shen Junwei
1Shanghai University of Medicine & Health Sciences, Shanghai, 201318 China.
2Tongji University affiliated Eastern Hospital, Shanghai, 200092 China.
Cell Death Discov. 2019 Mar 4;5:73. doi: 10.1038/s41420-019-0152-z. eCollection 2019.
As the most severe manifestation of coronary artery disease, myocardial infarction (MI) is a complex and multifactorial pathophysiologic process. However, the pathogenesis that underlies MI remains unclear. Here, we generated a MI mouse model by ligation of the proximal left anterior descending coronary artery. The transcriptome and proteome, at different time points after MI, were detected and analysed. Immune-related pathways, cell cycle-related pathways, and extracellular matrix remodelling-related pathways were significantly increased after MI. Not only innate immune cells but also adaptive immune cells participated in the early stage of MI. Proteins that functioned in blood agglutination, fibrinolysis, secretion, and immunity were significantly changed after MI. Nppa, Serpina3n, and Anxa1, three secreted proteins that can easily be detected in blood, were significantly changed after MI. Our discoveries not only reveal the molecular and cellular changes in MI but also identify potential candidate biomarkers of MI for clinical diagnosis or treatment.
作为冠状动脉疾病最严重的表现形式,心肌梗死(MI)是一个复杂的多因素病理生理过程。然而,心肌梗死的发病机制仍不清楚。在此,我们通过结扎左冠状动脉前降支近端建立了心肌梗死小鼠模型。检测并分析了心肌梗死后不同时间点的转录组和蛋白质组。心肌梗死后,免疫相关途径、细胞周期相关途径和细胞外基质重塑相关途径显著增加。不仅固有免疫细胞,而且适应性免疫细胞都参与了心肌梗死的早期阶段。心肌梗死后,在血液凝集、纤维蛋白溶解、分泌和免疫中起作用的蛋白质发生了显著变化。Nppa、Serpina3n和Anxa1这三种在血液中易于检测的分泌蛋白在心肌梗死后发生了显著变化。我们的发现不仅揭示了心肌梗死中的分子和细胞变化,还确定了心肌梗死潜在的候选生物标志物,用于临床诊断或治疗。