Ni Hanwen, Pan Wenqi, Jin Qi, Xie Yucai, Zhang Ning, Chen Kang, Lin Tianyou, Lin Changjian, Xie Yun, Wu Jiemin, Ni Peihua, Wu Liqun
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197# Ruijin Rd, Huangpu District, Shanghai, 200025, China.
Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197# Ruijin Rd, Huangpu District, Shanghai, 200025, China.
Clin Proteomics. 2021 Jan 6;18(1):1. doi: 10.1186/s12014-020-09304-8.
Atrial fibrillation (AF) is the most common cardiac heterogeneous rhythm disorder. It represents a major cause of mortality and morbidity, mainly related to embolic events and heart failure. Mechanisms of AF are complex and remain incompletely understood. Recent evidence suggests exosomes are membrane-coated objects released by many cell-types. Their presence in body fluids and the variable surface composition and content render them attractive as a mechanism for potential biomarkers. However, the content of serum exosomes of AF patients has not been fully delineated.
In this work, the serum exosomes from AF patients and healthy donors were used to compare changes in the exosome protein content. Exosomes were isolated from serum of AF patients and healthy donors and their purity was confirmed by Western blotting assays and transmission electron microscopy (TEM). Label-free LC-MS/MS quantitative proteomic analysis was applied to analyze protein content of serum exosomes.
A total of 440 exosomal protein groups were identified, differentially expressed proteins were filtrated with fold change ≥ 2.0 (AF/controls protein abundance ratio ≥ 2 or ≤ 0.5) and p value less than 0.05 (p < 0.05), significantly changed in abundance group contains 39 elevated proteins and 18 reduced proteins, while consistent presence/absence expression profile group contains 40 elevated proteins and 75 reduced proteins. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the anticoagulation, complement system and protein folding. Parallel-Reaction Monitoring Relative Quantitative Analysis (PRM) further suggested that AF related to complement system and protein folding.
These results revealed the composition and potential function of AF serum exosomes, thus providing a new perspective on the complement system and protein folding to AF.
心房颤动（AF）是最常见的心脏异质性节律紊乱。它是死亡率和发病率的主要原因，主要与栓塞事件和心力衰竭有关。AF的机制复杂，尚未完全了解。最近的证据表明，外泌体是由多种细胞类型释放的膜包被物体。它们在体液中的存在以及可变的表面组成和含量使其成为潜在生物标志物的一种有吸引力的机制。然而，AF患者血清外泌体的含量尚未完全阐明。
在这项研究中，使用AF患者和健康供体的血清外泌体来比较外泌体蛋白质含量的变化。从AF患者和健康供体的血清中分离出外泌体，并通过蛋白质免疫印迹分析和透射电子显微镜（TEM）确认其纯度。应用无标记液相色谱-串联质谱（LC-MS/MS）定量蛋白质组学分析来分析血清外泌体的蛋白质含量。
共鉴定出440个外泌体蛋白质组，差异表达蛋白经筛选，其变化倍数≥2.0（AF/对照蛋白丰度比≥2或≤0.5）且p值小于0.05（p＜0.05），丰度显著变化组包含39种上调蛋白和18种下调蛋白，而一致性存在/缺失表达谱组包含40种上调蛋白和75种下调蛋白。对外泌体差异蛋白的生物信息学分析证实了参与抗凝、补体系统和蛋白质折叠的成分显著富集。平行反应监测相对定量分析（PRM）进一步表明AF与补体系统和蛋白质折叠有关。
这些结果揭示了AF血清外泌体的组成和潜在功能，从而为AF的补体系统和蛋白质折叠提供了新的视角。
