老年急性心肌梗死病人冠状动脉的蛋白质翻译后修饰定量分析

Protein post-translational modification of coronary artery in elderly patients with acute myocardium infarction

目的 探索蛋白质翻译后修饰(post-translational modification, PTM)在人冠状动脉粥样硬化过程中的作用。方法 2例急性心肌梗死死亡病人的20个冠状动脉标本通过苏木精和伊红(HE)染色进行组织学分型,并提取蛋白质进行质谱分析,应用软件Peaks Studio X+对标本的质谱结果进行定量差异化分析。使用STRING网站进行蛋白质网络聚类分析、反应途径分析和基因本体功能富集等生物信息学分析。结果 20个冠状动脉样本中共鉴定出2819组蛋白和233种PTM方式。不同组织学分型标本有差异表达的蛋白质和PTM位点分别为123个和22个,22个差异修饰位点的修饰方式为氧化、乙酰化和脱酰胺化。生物信息学分析显示,差异蛋白和差异修饰主要与线粒体能量代谢高度相关。差异蛋白质网络聚类分析显示,线粒体ATP合成偶联质子转运网络最为富集,该网络包含ATP5A1、ATP5B、ATP5H和ATP5O 4种蛋白,4种蛋白的PTM丰度均在动脉粥样硬化早期阶段较高。结论 蛋白质PTM可能通过线粒体能量代谢影响人冠状动脉粥样硬化的发生发展,并在动脉粥样硬化的早期发挥重要作用。

Objective To explore the role of protein post-translational modification(PTM)in human coronary artery atherosclerosis.Methods Twenty coronary artery segments were collected from two elderly subjects dying from acute myocardium infarction.The hematoxylin and eosin(HE)staining was performed for pathological classification,and the human coronary arterial proteome and proteomics features were detected by means of mass spectrometry(MS)analysis.By means of Peaks Studio X+,further quantitative analysis was conducted.The STRING website was used for bioinformatics analysis,such as network cluster,reactome pathways and gene ontology(GO)functional enrichment analysis.Results A total of 2819 proteins and 233 types of PTM were identified in the 20 coronary artery segments.There were 123 differentially expressed proteins and 22 PTM modification sites,and the modifications of 22 sites included oxidation,acetylation and deamidation.Bioinformatics analysis showed that differential proteins and differential PTM sites were mainly highly correlated with mitochondrial energy metabolism.Cluster analysis of protein network showed that the mitochondrial adenosine triphosphate(ATP)synthesis coupled proton transport network was the most enriched,which included ATP5A1,ATP5B,ATP5H and ATP5O.The abundance of PTM of the four proteins was higher in the early stage of atherosclerosis.Conclusions Protein PTM may affect the development of human coronary atherosclerosis through mitochondrial energy metabolism and plays an important role in the early stage of atherosclerosis.