Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long‐term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in‐depth proteomics approach, including both semi‐quantitative and quantitative antibody arrays, was used to identify circulating biomarkers that may be associated with detrimental cardiac remodelling. Furthermore, statistical correlation analysis was performed between the candidate biomarkers and clinical cardiac remodelling data to demonstrate their clinical utility. A systematic proteomics approach revealed that sclerostin (SOST), growth differentiation factor‐15 (GDF‐15), urokinase‐type plasminogen activator (uPA), and midkine (MK) were increased, while monocyte chemotactic protein‐3 (MCP‐3) was uniquely decreased in MI patients who developed cardiac remodelling, compared to MI patients who did not develop cardiac remodelling and healthy humen. Moreover, correlation analyses between serum proteomes and cardiac remodelling echocardiographic parameters demonstrated a moderate positive association between left ventricular end‐diastolic volume index (LVEDVi) and the three serum proteins, uPA, MK and GDF‐15 (P < .05, respectively), and a moderate negative correlation between LV ejection fraction (LVEF) and these serum proteins (P < .05, respectively). Importantly, uPA and MK were firstly identified to be associated with the development of cardiac remodelling. The present study contributes to a better understanding of the various cytokines expressed during adverse cardiac remodelling. The identified biomarkers may facilitate early identification of patients at high risk of ischaemic heart failure pending further confirmation through larger clinical trials.

中文翻译：

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深入的蛋白质组学方法揭示了心肌梗死后心脏重构的新生物标志物：一项探索性分析。

心肌梗死（MI）后的心脏重塑是与进行性心力衰竭相关的适应不良改变，并损害了长期临床结果。大部分受MI折磨的患者仍会出现与心脏重塑相关的不良结局。因此，对于早期预测心脏重塑的生物标志物的识别至关重要。使用包括半定量和定量抗体阵列在内的深入蛋白质组学方法来鉴定可能与有害心脏重塑有关的循环生物标志物。此外，在候选生物标志物和临床心脏重塑数据之间进行了统计相关性分析，以证明其临床实用性。系统的蛋白质组学方法表明，硬化蛋白（SOST），在发生心脏重塑的MI患者中，生长分化因子15（GDF-15），尿激酶型纤溶酶原激活剂（uPA）和中期因子（MK）升高，而单核细胞趋化蛋白3（MCP-3）则独特降低，与没有发展心脏重塑和健康人体的MI患者相比。此外，血清蛋白质组学与心脏重塑超声心动图参数之间的相关性分析表明，左心室舒张末期容积指数（LVEDVi）与三种血清蛋白uPA，MK和GDF-15之间存在中等程度的正相关（与没有发展心脏重塑和健康人体的MI患者相比。此外，血清蛋白质组学与心脏重塑超声心动图参数之间的相关性分析表明，左心室舒张末期容积指数（LVEDVi）与三种血清蛋白uPA，MK和GDF-15之间存在中等程度的正相关（与没有发展心脏重塑和健康人体的MI患者相比。此外，血清蛋白质组学与心脏重塑超声心动图参数之间的相关性分析表明，左心室舒张末期容积指数（LVEDVi）与三种血清蛋白uPA，MK和GDF-15之间存在中等程度的正相关（ 分别为P <.05和LV射血分数（LVEF）与这些血清蛋白之间的中等负相关（ 分别为P <.05）。重要的是，首先确定uPA和MK与心脏重塑的发展有关。本研究有助于更好地了解不良心脏重塑过程中表达的各种细胞因子。所识别的生物标记物可能有助于早期识别处于缺血性心力衰竭高风险的患者，等待通过较大的临床试验进一步确认。