Cardiac rupture (CR) is a rare but catastrophic mechanical complication of acute myocardial infarction (AMI) that seriously threatens human health. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of CR has yet to be elucidated. In the present study, a quantitative approach with tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry was used to characterize the differential protein expression profiles of patients with CR. Plasma samples were collected from patients with CR (n = 37), patients with AMI (n = 47), and healthy controls (n = 47). Candidate proteins were selected for validation by multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA). In total, 1208 proteins were quantified and 958 differentially expressed proteins (DEPs) were identified. The difference in the expression levels of the DEPs was more noticeable between the CR and Con groups than between the AMI and Con groups. Bioinformatics analysis showed most of the DEPs to be involved in numerous crucial biological processes and signaling pathways, such as RNA transport, ribosome, proteasome, and protein processing in the endoplasmic reticulum, as well as necroptosis and leukocyte transendothelial migration, which might play essential roles in the complex pathological processes associated with CR. MRM analysis confirmed the accuracy of the proteomic analysis results. Four proteins i.e., C-reactive protein (CRP), heat shock protein beta-1 (HSPB1), vinculin (VINC) and growth/differentiation factor 15 (GDF15), were further validated via ELISA. By receiver operating characteristic (ROC) analysis, combinations of these four proteins distinguished CR patients from AMI patients with a high area under the curve (AUC) value (0.895, 95% CI, 0.802–0.988, p < 0.001). Our study highlights the value of comprehensive proteomic characterization for identifying plasma proteome changes in patients with CR. This pilot study could serve as a valid foundation and initiation point for elucidation of the mechanisms of CR, which might aid in identifying effective diagnostic biomarkers in the future.

中文翻译：

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使用基于 TMT 的定量蛋白质组学方法对急性心肌梗死后心脏破裂患者的血浆蛋白进行蛋白质组学分析

心脏破裂（CR）是急性心肌梗死（AMI）一种罕见但灾难性的机械并发症，严重威胁人类健康。然而，用于临床诊断的可靠生物标志物和 CR 的潜在信号通路见解尚未阐明。在本研究中，采用串联质量标签（TMT）标记和液相色谱-串联质谱的定量方法来表征 CR 患者的差异蛋白表达谱。血浆样本采集自 CR 患者 (n = 37)、AMI 患者 (n = 47) 和健康对照 (n = 47)。通过多重反应监测 (MRM) 和酶联免疫吸附测定 (ELISA) 选择候选蛋白进行验证。总共对 1208 种蛋白质进行了定量，并鉴定了 958 种差异表达蛋白质 (DEP)。CR 组和 Con 组之间 DEP 表达水平的差异比 AMI 和 Con 组之间更明显。生物信息学分析显示，大多数DEP参与许多重要的生物过程和信号通路，例如内质网中的RNA运输、核糖体、蛋白酶体和蛋白质加工，以及坏死性凋亡和白细胞跨内皮迁移，可能发挥重要作用与 CR 相关的复杂病理过程。MRM分析证实了蛋白质组分析结果的准确性。通过 ELISA 进一步验证了四种蛋白质，即 C 反应蛋白 (CRP)、热休克蛋白 beta-1 (HSPB1)、纽蛋白 (VINC) 和生长/分化因子 15 (GDF15)。通过受试者工作特征 (ROC) 分析，这四种蛋白的组合可通过高曲线下面积 (AUC) 值（0.895，95% CI，0.802–0.988，p < 0.001）区分 CR 患者和 AMI 患者。我们的研究强调了综合蛋白质组表征对于识别 CR 患者血浆蛋白质组变化的价值。这项试点研究可以作为阐明 CR 机制的有效基础和起点，这可能有助于将来识别有效的诊断生物标志物。