Abstract：
OBJECTIVE: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
METHODS: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
RESULTS: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
CONCLUSIONS: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
METHODS: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
RESULTS: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
CONCLUSIONS: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
摘要：
目的：尽管晚期心力衰竭（HF）的临床后果在不同的心肌病病因中可能相似，它们的蛋白质组表达可能显示出与潜在病理生理学相关的实质性差异。我们旨在确定不同病因的非缺血性心肌病中基于心肌组织的蛋白质组学特征和潜在的分子病理生理学。
方法：对9例经活检证实的非缺血性心肌病（3例扩张型心肌病[DCM]，2肥厚型心肌病[HCM]，和4个心肌炎）以及使用串联质量标签与液相色谱-质谱联用的五个对照。差异蛋白表达分析,基因本体论（GO）分析，和创造性途径分析(IPA)进行以鉴定与对照相比每种心肌病类型的蛋白质组差异和分子机制。根据临床和病理结果进一步评估蛋白质组学特征。
结果：主成分分析得分图显示对照组，DCM,HCM聚集良好。然而,心肌炎样本呈分散分布。IPA揭示了DCM和HCM中氧化磷酸化的下调和沉默调节蛋白信号通路的上调。随着RhoGDP解离抑制剂的下调，各种炎症途径在心肌炎中上调。通过广泛的蛋白质组学分析鉴定的分子病理生理学代表了具有丰富蛋白质组的每种心肌病的临床和病理特性。
结论：晚期HF患者非缺血性心肌病的不同病因表现出不同的蛋白质组学表达，尽管有共同的病理结果。考虑到非缺血性晚期HF中不同蛋白质组表达的定制管理策略的益处需要进一步研究。
方法：对9例经活检证实的非缺血性心肌病（3例扩张型心肌病[DCM]，2肥厚型心肌病[HCM]，和4个心肌炎）以及使用串联质量标签与液相色谱-质谱联用的五个对照。差异蛋白表达分析,基因本体论（GO）分析，和创造性途径分析(IPA)进行以鉴定与对照相比每种心肌病类型的蛋白质组差异和分子机制。根据临床和病理结果进一步评估蛋白质组学特征。
结果：主成分分析得分图显示对照组，DCM,HCM聚集良好。然而,心肌炎样本呈分散分布。IPA揭示了DCM和HCM中氧化磷酸化的下调和沉默调节蛋白信号通路的上调。随着RhoGDP解离抑制剂的下调，各种炎症途径在心肌炎中上调。通过广泛的蛋白质组学分析鉴定的分子病理生理学代表了具有丰富蛋白质组的每种心肌病的临床和病理特性。
结论：晚期HF患者非缺血性心肌病的不同病因表现出不同的蛋白质组学表达，尽管有共同的病理结果。考虑到非缺血性晚期HF中不同蛋白质组表达的定制管理策略的益处需要进一步研究。
