Key Discipline of Integrated Chinese and Western Medicine, Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
J Cell Mol Med. 2020 Sep;24(17):10042-10051. doi: 10.1111/jcmm.15611. Epub 2020 Jul 23.
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.
心肌梗死后的心脏重构是一种与进行性心力衰竭相关的适应性改变，会影响长期临床结局。相当一部分心肌梗死后的患者仍会出现与心脏重构相关的不良结局。因此，识别心脏重构的早期预测标志物至关重要。本研究采用深入的蛋白质组学方法，包括半定量和定量抗体阵列，以鉴定可能与不良心脏重构相关的循环生物标志物。此外，还对候选生物标志物与临床心脏重构数据之间的相关性进行了统计分析，以证明其临床应用价值。系统的蛋白质组学方法显示，在发生心脏重构的心肌梗死患者中，骨硬化蛋白（SOST）、生长分化因子 15（GDF-15）、尿激酶型纤溶酶原激活物（uPA）和中期因子（MK）升高，而单核细胞趋化蛋白 3（MCP-3）降低。与未发生心脏重构和健康人群的心肌梗死患者相比。此外，血清蛋白质组学与心脏重构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）与血清中三种蛋白质 uPA、MK 和 GDF-15 之间存在中度正相关（P<.05），左心室射血分数（LVEF）与这些血清蛋白之间存在中度负相关（P<.05）。重要的是，首次发现 uPA 和 MK 与心脏重构的发生有关。本研究有助于更好地了解不良心脏重构过程中表达的各种细胞因子。所鉴定的生物标志物可能有助于早期识别发生缺血性心力衰竭风险较高的患者，进一步的大型临床试验可对其进行验证。
