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综合血浆代谢组学和脂质组学分析揭示心力衰竭的潜在生物标志物。

Comprehensive plasma metabolomic and lipidomic analyses reveal potential biomarkers for heart failure.

机构信息

Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Hua Yuan North Rd, Hai Dian District, Beijing, 100191, China.

Center of Medical and Health Analysis, Peking University Health Science Center, Beijing, 100191, China.

出版信息

Mol Cell Biochem. 2021 Sep;476(9):3449-3460. doi: 10.1007/s11010-021-04159-5. Epub 2021 May 11.

Abstract

Heart failure is a syndrome with symptoms or signs caused by cardiac dysfunction. In clinic, four stages (A, B, C, and D) were used to describe heart failure progression. This study was aimed to explore plasma metabolomic and lipidomic profiles in different HF stages to identify potential biomarkers. Metabolomics and lipidomics were performed using plasma of heart failure patients at stages A (n = 49), B (n = 61), and C+D (n = 26). Analysis of Variance (ANOVA) was used for screening dysregulated molecules. Bioinformatics was used to retrieve perturbed metabolic pathways. Univariate and multivariate receiver operating characteristic curve (ROC) analyses were used for potential biomarker screening. Stage A showed significant difference to other stages, and 142 dysregulated lipids and 134 dysregulated metabolites were found belonging to several metabolic pathways. Several marker panels were proposed for the diagnosis of heart failure stage A versus stage B-D. Several molecules, including lysophosphatidylcholine 18:2, cholesteryl ester 18:1, alanine, choline, and Fructose, were found correlated with B-type natriuretic peptide or left ventricular ejection fractions. In summary, using untargeted metabolomic and lipidomic profiling, several dysregulated small molecules were successfully identified between HF stages A and B-D. These molecules would provide valuable information for further pathological researches and biomarker development.

摘要

心力衰竭是一种由心脏功能障碍引起的症状或体征的综合征。临床上,采用 A、B、C 和 D 四个阶段来描述心力衰竭的进展。本研究旨在探讨不同心力衰竭阶段的血浆代谢组学和脂质组学特征,以识别潜在的生物标志物。使用心力衰竭患者 A 期(n=49)、B 期(n=61)和 C+D 期(n=26)的血浆进行代谢组学和脂质组学分析。采用方差分析(ANOVA)筛选失调分子。生物信息学用于检索失调的代谢途径。单变量和多变量受试者工作特征曲线(ROC)分析用于潜在生物标志物的筛选。A 期与其他阶段有显著差异,发现了 142 种失调脂质和 134 种失调代谢物,它们属于几种代谢途径。提出了几个用于诊断心力衰竭 A 期与 B-D 期的标志物组合。包括溶血磷脂酰胆碱 18:2、胆固醇酯 18:1、丙氨酸、胆碱和果糖在内的几种分子与 B 型利钠肽或左心室射血分数有关。总之,通过非靶向代谢组学和脂质组学分析,成功地在心力衰竭 A 期和 B-D 期之间鉴定了几种失调的小分子。这些分子将为进一步的病理研究和生物标志物开发提供有价值的信息。

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