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Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

ABSTRACT: Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are common causes of heart failure (HF). Though they share similar clinical characteristics, their differential effects on cardiovascular metabolomics have yet to be elucidated. In this study, we applied a comprehensive metabolomics platform to plasma samples of HF patients with different etiology (38 patients with DCM and 18 patients with ICM) and 20 healthy controls. Significant differences in metabolomics profiling were shown among two cardiomyopathy groups and healthy controls. Two hundred thirty three dysregulated metabolites were identified between DCM vs. healthy controls, and 204 dysregulated metabolites between ICM patients and healthy controls. They have 140 metabolites in common, with fold-changes in the same direction in both groups. Pathway analysis found the commonalities of HF pathways as well as disease-specific metabolic signatures. In addition, we found that a combination panel of 6 metabolites including 1-pyrroline-2-carboxylate, norvaline, lysophosphatidylinositol (16:0/0:0), phosphatidylglycerol (6:0/8:0), fatty acid esters of hydroxy fatty acid (24:1), and phosphatidylcholine (18:0/18:3) may have the potential to differentiate patients with DCM and ICM.

SUBMITTER: Zhao J

PROVIDER: S-EPMC7683512 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

Zhao Junhan J Yang Shengwen S Jing Ran R Jin Han H Hu Yiran Y Wang Jing J Gu Min M Niu Hongxia H Zhang Shu S Chen Liang L Hua Wei W

Frontiers in cardiovascular medicine 20201110

Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are common causes of heart failure (HF). Though they share similar clinical characteristics, their differential effects on cardiovascular metabolomics have yet to be elucidated. In this study, we applied a comprehensive metabolomics platform to plasma samples of HF patients with different etiology (38 patients with DCM and 18 patients with ICM) and 20 healthy controls. Significant differences in metabolomics profiling were shown amon ...[more]

PMID: 33240942

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Project description:BackgroundIschemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar clinical manifestations but differ in pathogenesis. We aimed to identify T cell-associated serum markers that can be used to distinguish between ICM and DCM.MethodsWe identified differentially expressed genes (DEGs) with transcriptome sequencing data in GSE116250, and then conducted enrichment analysis of DEGs in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were used to analyze the relationship between T cells-related genes and identify hub genes. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect T cell-associated proteins in serum, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of these serum markers.ResultsUsing the limma package and Venn plots, we found that the non-failing donors (NFD) and DCM groups shared many of the same DEGs and DEGs-enriched functions compared to the ICM group, which were involved in T cell activation and differentiation, among other functions. Subsequently, the immune cell score showed no difference between NFD and DCM, but they were significantly different from ICM patients in CD8 T cells CD4 T cells memory resting and activated, T cells follicular helper, and M1 macrophage. After analyzing T cell-associated DEGs, it was found that 4 DEGs encoding secreted proteins were highly expressed in the ICM group compared with the NFD and DCM groups, namely chemokine (C-C motif) ligand 21 (CCL21), interleukin (IL)-1β, lymphocyte-activation gene 3 (LAG3), and vascular cell adhesion molecule-1 (VCAM-1). Importantly, the serum levels of CCL21, IL-1β, LAG3, and VCAM-1 in ICM patients were all significantly higher than those in DCM patients. The ROC curves showed that the area under the curve (AUC) values of serum CCL21, IL-1β, LAG3, and VCAM-1 were 0.775, 0.868, 0.934, and 0.903, respectively.ConclusionsWe have identified four T cell-associated serum markers, CCL21, IL-1β, LAG3, and VCAM-1, as potential diagnostic serum markers that differentiate ICM from DCM.

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Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

Publications

Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

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