Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany; Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
J Proteomics. 2019 Oct 30;209:103508. doi: 10.1016/j.jprot.2019.103508. Epub 2019 Aug 30.
To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction. The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital. SIGNIFICANCE: Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.
为了确定支持更好表型分析的潜在生物标志物，并深入了解扩张型心肌病（DCM）的病理生理学，本研究通过质谱法比较分析了 DCM 患者与左心室射血分数（LVEF）低正常和正常个体的血浆蛋白谱。使用 MARS Hu-6 柱耗尽血浆后，使用 LTQ-Orbitrap Velos 质谱仪进行全局蛋白质组谱分析。为了比较和确认结果，研究了两个不同的样本发现集。差异丰度蛋白涉及脂质代谢、凝血和急性期反应。在第三个独立的患者队列中，通过靶向蛋白分析验证了血清对氧磷酶 1（PON1）、胱抑素 C、溶菌酶 C、载脂蛋白 A-II 和载脂蛋白 M。此外，还通过 ELISA 测定了 PON1 水平。这些数据突出了 PON1 作为区分 DCM 患者的潜在标志物，不仅与 LVEF 正常的患者不同，而且与射血分数保留的心力衰竭患者也不同。这些结果突出了脂质代谢和炎症作为与心肌炎症可疑入院患者相比，DCM 患者发生改变的主要途径。意义：多项研究集中于鉴定血液浆中与心力衰竭（HF）相关的蛋白质特征，但只有少数研究主要基于考虑特定 HF 病理的小样本系列。因此，我们对较大样本的个体进行了比较性的全血浆蛋白质谱分析，这些个体的左心室射血分数（LVEF）降低，分为扩张型心肌病患者和 LVEF 正常但表现出可疑心肌炎的个体。DCM 患者显示出参与脂质代谢、凝血和急性期反应的蛋白质水平发生改变。通过在独立的患者队列中进行靶向蛋白分析，对最可靠的候选物，如血清对氧磷酶 1（PON1）、胱抑素 C、溶菌酶 C、载脂蛋白 A-II 和载脂蛋白 M 进行了验证。还通过 ELISA 测定了 PON1 水平。这些数据突出了 PON1 作为区分 DCM 患者的潜在标志物，不仅与 LVEF 正常的患者不同，而且与射血分数保留的心力衰竭患者也不同。
