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.

中文翻译：

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阵发性房颤患者血清外泌体的无标记蛋白质组学分析

心房颤动（AF）是最常见的心脏异质性心律失常。它代表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。房颤的机制很复杂，仍未完全了解。最近的证据表明，外泌体是许多细胞类型释放的被膜包裹的物体。它们在体液中的存在以及表面成分和含量的变化使它们作为潜在生物标志物的一种机制具有吸引力。然而，房颤患者血清外泌体的含量尚未完全描述。在这项工作中，AF患者和健康供体的血清外泌体用于比较外泌体蛋白质含量的变化。从房颤患者和健康供体的血清中分离出外泌体，并通过蛋白质印迹分析和透射电子显微镜（TEM）证实了其纯度。无标记LC-MS / MS定量蛋白质组学分析用于分析血清外泌体的蛋白质含量。总共鉴定出440个外泌体蛋白组，差异表达蛋白经倍数变化≥2.0（AF /对照蛋白丰度比≥2或≤0.5）过滤且p值小于0.05（p <0.05）包含39个升高的蛋白和18个还原的蛋白，而一致的存在/不存在表达谱组包含40个升高的蛋白和75个还原的蛋白。差异性外泌体蛋白的生物信息学分析证实，抗凝相关成分的显着富集，补体系统和蛋白质折叠。平行反应监测相对定量分析（PRM）进一步表明房颤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。