射血分数降低的心力衰竭患者心房颤动相关的蛋白质组学生物标志物和生物学途径

IF 2.9 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart Rhythm O2 Pub Date : 2025-09-01 DOI:10.1016/j.hroo.2025.06.007

Teun B. Petersen MSc , Mylène Barry-Loncq de Jong MD , Jie Fen Chin MD , Navin Suthahar MD, PhD , Peter J. van der Spek PhD , Peter D. Katsikis MD, PhD , K. Martijn Akkerhuis MD, PhD , Victor A. Umans MD, PhD , Rudolf A. de Boer MD, PhD , Bas M. van Dalen MD, PhD , Jasper J. Brugts MD, PhD , Folkert W. Asselbergs MD, PhD , Eric Boersma PhD , Dimitris Rizopoulos PhD , Sing-Chien Yap MD, PhD , Isabella Kardys MD, PhD

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引用次数: 0

摘要

房颤（AF）和心力衰竭（HF）是交织在一起的高死亡率和影响生活质量的疾病。HF合并心房颤动患者与不合并心房颤动患者的生物学机制可能不同。目的本研究旨在描述伴有和不伴有房颤的HF伴射血分数降低（HFrEF）患者中循环蛋白与病理生理效应的差异。方法我们检测了377例伴射血分数降低（HFrEF）患者，并使用基于适体的多重蛋白质组学方法测量了基线血液样本中的4210种循环蛋白。房颤（房颤史或基线心电图）与蛋白质之间的关系通过调整年龄、性别、肾功能和基线时心衰持续时间的回归模型进行评估。利用富集分析评估af相关蛋白与生物过程的关联。结果中位年龄[25 - 75个百分点]为64岁[55-72]，73%[377例中274例]为男性，28%[375例中104例]为纽约心脏协会III/IV级，37%[377例中139例]为房颤（房颤史[36%，377例中137例]或基线心电图房颤[8%，374例中30例]）。我们发现71种与房颤显著相关的蛋白（错误发现率<； 05），包括房颤区域中研究较多的蛋白（如肌钙蛋白T、胰岛素样生长因子结合蛋白7、微纤维相关糖蛋白4、骨形态发生蛋白10、血管生成素2）和较少研究的蛋白（如嗅觉蛋白样蛋白3、角化蛋白、基底蛋白）。我们的通路分析揭示了与各种潜在机制相关的蛋白质模块，如神经系统发育、弹性纤维组装、蛋白质糖基化和醚类脂质代谢。结论HFrEF合并心房颤动患者具有不同的循环蛋白质组学特征，这些差异与多种生物学机制有关。本研究概述了HFrEF患者与房颤相关的系统生物学途径，证实了房颤相关蛋白的（预）临床发现，并可以在仔细验证后为未来新的治疗靶点和HFrEF-AF管理的研究提供信息。

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Proteomic biomarkers and biological pathways associated with atrial fibrillation in heart failure patients with reduced ejection fraction

Background

Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality and impact on quality of life. The biological mechanisms at play in patients with HF with vs without AF may differ.

Objectives

This study aimed to describe differences in circulating proteins with putative pathophysiological effects between HF with reduced ejection fraction (HFrEF) patients with and without AF.

Methods

We examined 377 patients with ambulant HFrEF and measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (AF history or on baseline electrocardiogram) and the proteins were assessed using regression models adjusted for age, sex, kidney function, and duration of HF at baseline. Associations of AF-related proteins with biological processes were evaluated using enrichment analyses.

Results

The median age [25th–75th percentile] was 64 years [55–72], 73% [274 of 377] were male, 28% [104 of 375] had New York Heart Association class III/IV, and 37% [139 of 377] had AF (either AF history [36%, 137 of 377] or AF on baseline electrocardiogram [8%, 30 of 374]). We found 71 proteins significantly associated with AF (false discovery rate < .05), including well-studied (eg, troponin T, insulin-like growth factor-binding protein 7, microfibril-associated glycoprotein 4, bone morphogenetic protein 10, angiopoietin 2) and lesser-studied proteins (eg, olfactomedin−like protein 3, keratocan, basigin) in the AF domain. Our pathway analysis revealed modules of proteins related to various underlying mechanisms, such as nervous system development, elastic fiber assembly, protein glycosylation, and ether lipid metabolism.

Conclusions

Patients with HFrEF with AF have distinct circulating proteomic profiles, and these differences are related to various biological mechanisms. This study provides an overview of the systemic biological pathways associated with AF in patients with HFrEF, confirms (pre-)clinical findings regarding AF-related proteins, and could inform future research in novel treatment targets and HFrEF-AF management after careful validation.

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来源期刊

Heart Rhythm O2 Cardiology and Cardiovascular Medicine

CiteScore

3.30

自引率

0.00%

发文量

审稿时长

52 days