Identification of serum C4BPA as a potential diagnostic marker of right ventricular remodelling via proteomic analysis

IF 3.7 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

ESC Heart Failure Pub Date : 2025-04-16 DOI:10.1002/ehf2.15292

Xuenan Wang, Cheng Yu, Meiling Li, Huiling Cai, Yongjian Yang, Cong Lan

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引用次数: 0

Abstract

Aims

Right ventricular (RV) remodelling, a progressive condition characterized by maladaptive cardiac structural and functional changes, primarily results from prolonged pressure overload in patients with pulmonary hypertension (PH). Accurate, universal and easy-to-use biomarkers for assessing the severity of RV remodelling are lacking. This study aimed to identify serum proteins as potential biomarkers of RV remodelling using high-throughput proteomic analysis-based screening.

Methods

Sprague–Dawley rats were subjected to sham surgery (control group) or pulmonary artery banding for 4 weeks with 2.3-mm diameter and 1.8-mm diameter rubber rings to induce mild and severe RV modelling, respectively. Serum proteomic profiling revealed 170 differentially expressed serum proteins (DEPs) among the three groups, and three DEPs gradually increased with worsening RV remodelling. Among the three DEPs, C4b-binding protein alpha chain (C4BPA) exhibited the highest upregulation in the severe group (6.93 vs. 16.5 ng/mL, P < 0.001), and linear regression analysis revealed a negative correlation between serum C4BPA levels and tricuspid annular plane systolic excursion (TAPSE) in rats [beta = −0.78, 95% confidence interval (CI) −14.5 to −7.11, P < 0.001]. The diagnostic power of C4BPA was further validated in 127 patients (34 with adaptive RV pressure overload, 36 with maladaptive RV pressure overload, 32 with left ventricular hypertrophy and 25 controls). Control and left ventricular hypertrophy patients exhibited lower serum C4BPA levels than the two RV groups, and serum C4BPA levels were higher in patients with maladaptive RV than in those with adaptive RV (754 vs. 524 pg/mL, P < 0.001). Linear regression analysis revealed a negative correlation between serum C4BPA levels and TAPSE in PH patients. The predictive power of C4BPA for maladaptive RV function in PH patients, indicated by receiver operating characteristic analysis (cut-off value 573 pg/mL, area under the curve 0.792), was as good as that of B-type natriuretic peptide (BNP). High serum C4BPA levels (≥573 pg/mL) were associated with lower TAPSE/pulmonary arterial systolic pressure ratios (P < 0.001) and higher BNP levels (P < 0.001).

Conclusions

Serum C4BPA may represent a novel diagnostic biomarker for RV pathological remodelling associated with RV maladaptation in PH patients.

Abstract Image

查看原文本刊更多论文

通过蛋白质组学分析鉴定血清C4BPA作为右心室重构的潜在诊断标志物。

目的：右心室重构是一种以心脏结构和功能改变不适应为特征的进行性疾病，主要是由肺动脉高压（PH）患者的长期压力过载引起的。目前还缺乏准确、通用和易于使用的生物标志物来评估右心室重构的严重程度。本研究旨在通过基于高通量蛋白质组学分析的筛选，确定血清蛋白作为RV重塑的潜在生物标志物。方法：对Sprague-Dawley大鼠进行假手术（对照组）或用直径2.3 mm、直径1.8 mm的橡胶环捆扎肺动脉4周，分别建立轻度和重度RV模型。血清蛋白质组学分析显示，三组患者血清中有170个差异表达蛋白（DEPs），其中3个差异表达蛋白随着RV重构的恶化而逐渐增加。在这三种DEPs中，c4b结合蛋白α链（C4BPA）在严重组中表现出最高的上调（6.93 vs. 16.5 ng/mL， P）。结论：血清C4BPA可能是PH患者与RV适应不良相关的RV病理重塑的一种新的诊断生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine

CiteScore

7.00

自引率

7.90%

发文量

461

审稿时长

12 weeks

期刊介绍： ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.