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心房颤动患者的蛋白质组学特征为诊断提供了候选生物标志物。

Proteomic profiles of patients with atrial fibrillation provide candidate biomarkers for diagnosis.

机构信息

Shanghai Medical College, Fudan University, Shanghai 200032, China..

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

出版信息

Int J Cardiol. 2021 Dec 1;344:205-212. doi: 10.1016/j.ijcard.2021.09.047. Epub 2021 Sep 28.

Abstract

BACKGROUND

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide with an increasing risk of heart failure, stroke, and thromboembolic events. Currently distinct pathophysiological mechanisms during AF development and valuable biomarkers for AF management remain unknown.

METHODS

In this study, we collected peripheral plasma samples from 18 non-valvular AF patients and 10 controls. A LC-MS/MS-DIA-based quantitative proteomic analysis, as well as bioinformatic analysis, was performed for discovery of differentially expressed proteins (DEPs) and dysregulated pathways. Next, we utilized enzyme-linked immunosorbent assay (ELISA) to validate selected DEPs and assessed their abilities for discrimination in another group of 20 AF patients and 10 controls.

RESULTS

The plasma proteome provided evidence for vital roles of abnormal inflammation, hemostasis, tissue remodeling and metabolism in AF patients. Differences between paroxysmal and persistent AF mainly lie in proteins or pathways related to hemostasis and cardiac remodeling. In addition, we successfully validated up-regulated proteins of platelet factor 4 variant 1 (PF4V1), thrombospondin-1 (THBS1), platelet basic protein (PBP) and fructose-bisphosphate aldolase A (ALDOA) in another group, which could make discrimination between AF patients and controls.

CONCLUSIONS

Our pilot proteomic study provided candidate biomarkers of PF4V1, THBS1, PBP and ALODA with the hope of application in AF management. And we showed the differences in pathophysiological mechanisms between paroxysmal and persistent AF. They mainly focused on pathways of hemostasis and cardiac remodeling, which could be a valuable clue for further research on AF progression.

摘要

背景

心房颤动(AF)是全球最常见的心律失常,心力衰竭、中风和血栓栓塞事件的风险增加。目前,AF 发展过程中的明确病理生理机制和有价值的 AF 管理生物标志物仍不清楚。

方法

在这项研究中,我们收集了 18 名非瓣膜性 AF 患者和 10 名对照者的外周血浆样本。进行了基于 LC-MS/MS-DIA 的定量蛋白质组学分析以及生物信息学分析,以发现差异表达蛋白(DEPs)和失调途径。接下来,我们利用酶联免疫吸附试验(ELISA)验证了选定的 DEPs,并评估了它们在另一组 20 名 AF 患者和 10 名对照者中的鉴别能力。

结果

血浆蛋白质组为 AF 患者异常炎症、止血、组织重塑和代谢的重要作用提供了证据。阵发性和持续性 AF 之间的差异主要在于与止血和心脏重塑相关的蛋白质或途径。此外,我们在另一组中成功验证了血小板因子 4 变体 1(PF4V1)、血小板反应蛋白 1(THBS1)、血小板碱性蛋白(PBP)和果糖二磷酸醛缩酶 A(ALDOA)的上调蛋白,它们可以区分 AF 患者和对照组。

结论

我们的初步蛋白质组学研究提供了 PF4V1、THBS1、PBP 和 ALODA 的候选生物标志物,有望应用于 AF 的管理。我们还显示了阵发性和持续性 AF 之间在病理生理机制上的差异。它们主要集中在止血和心脏重塑途径上,这可能为 AF 进展的进一步研究提供有价值的线索。

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