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Abstract：
Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein-metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.
摘要：
扩张型心肌病（DCM）的特征是左心室射血分数（LVEF）降低和左心室或双心室扩张。我们评估了DCM中循环蛋白和代谢物与结构和功能心脏参数的性别特异性关联。血浆样本（297名男性，71名女性）使用Olink测定（靶向分析）或LC-MS/MS（非靶向分析）分析蛋白质，和代谢物使用LCMS/MS(BiocratesAbsoluteIDQp180试剂盒)。蛋白质（n=571）或代谢物（n=163）与LVEF的关联，测量左心室舒张末期直径（LVEDD测量），和LVEDD相对于标准值的扩张百分比(LVEDDacc。对HENRY)在组合和性别特异性回归模型中进行了检查。为了揭示蛋白质-代谢物的关系，进行相关分析。蛋白质之间的关联，代谢物和LVEF仅限于男性，而男女均不存在与LVEDD的关联。在第二个独立的DCM队列(93名男性)中验证了显著的代谢物。综合分析表明，改变的蛋白质和参与脂质代谢的代谢物之间存在密切关系，炎症,和内皮功能障碍与LVEF下降，犬尿氨酸是最突出的发现。在DCM中，心脏功能的丧失由具有性别特异性差异的循环蛋白和代谢物反映.我们的综合方法表明，同时评估特定的蛋白质和代谢物可能有助于我们深入了解与DCM相关的改变。
