Tonry Claire, Linden Katie, Collier Patrick, Ledwidge Mark, McDonald Ken, Collins Ben C, Watson Chris J
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
Department of Cardiovascular Medicine, Cleveland Clinic, OH 44195, USA.
Biomedicines. 2024 Aug 1;12(8):1712. doi: 10.3390/biomedicines12081712.
Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients. HCM had a diverse proteomic profile compared to that of DCM and ISCM. Differentially expressed proteins unique to HCM were identified based on an observed fold change of ≥1.5 or ≤0.67 and q-value ≤ 0.05. Candidate proteins of interest were found to be significantly associated with clinical features of HCM. The significant association between these proteins and HCM was validated in an independent dataset. This represents one of the largest and deepest proteomic datasets for myocardial tissue reported to date. The dataset highlights the diverse proteomic profile of HCM, relative to other cardiomyopathies, and reveals disease-relevant pathways and promising biomarker candidates that are uniquely associated with HCM.
肥厚型心肌病（HCM）是一种早期难以诊断的疾病，迫切需要更有效的治疗方案。本研究的目的是比较HCM与缺血性心肌病（ISCM）和扩张型心肌病（DCM）的分子特征，以确定能够支持开发更好的HCM诊断和治疗方案的蛋白质和信号通路靶点。应用高通量质谱工作流程，以实现对HCM、DCM、ISCM和非心力衰竭对照患者左心室组织的深度定量覆盖。与DCM和ISCM相比，HCM具有多样的蛋白质组学特征。基于观察到的≥1.5或≤0.67的倍数变化和q值≤0.05，鉴定出HCM特有的差异表达蛋白质。发现感兴趣的候选蛋白质与HCM的临床特征显著相关。这些蛋白质与HCM之间的显著关联在一个独立的数据集中得到了验证。这是迄今为止报道的最大、最深的心肌组织蛋白质组学数据集之一。该数据集突出了HCM相对于其他心肌病的多样蛋白质组学特征，并揭示了与疾病相关的信号通路和与HCM独特相关的有前景的生物标志物候选物。
