Metabolic Processes are Potential Biological Processes Distinguishing Nonischemic Dilated Cardiomyopathy from Ischemic Cardiomyopathy: A Clue from Serum Proteomics

Abstract

Guangyong Huang,1 Zhiqi Huang,2 Yunling Peng,1 Yuehai Wang,1 Weitao Liu,1 Yuzeng Xue,1 Wenbo Yang3 1Department of Cardiology, Liaocheng People’s Hospital of Shandong University, Liaocheng, People’s Republic of China; 2Department of Geriatric Medicine, Civil Aviation General Hospital, Beijing, People’s Republic of China; 3Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Wenbo YangDepartment of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM) are the two most common causes of heart failure. However, our understanding of the specific proteins and biological processes distinguishing DCM from ICM remains insufficient.Materials and Methods: The proteomics analyses were performed on serum samples from ICM (n=5), DCM (n=5), and control (n=5) groups. Proteomics and bioinformatics analyses, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA), were performed to identify the hub circulating proteins and the hub biological processes in ICM and DCM.Results: The analysis of differentially expressed proteins and WGCNA identified the hub circulating proteins in ICM (GAPDH, CLSTN1, VH3, CP, and ST13) and DCM (one downregulated protein, FGG; 18 upregulated proteins, including HEL-S-276, IGK, ALDOB, HIST1H2BJ, HEL-S-125m, RPLP2, EL52, NCAM1, P4HB, HEL-S-99n, HIST1H4L, HIST2H3PS2, F8, ERP70, SORD, PSMA3, PSMB6, and PSMA6). The mRNA expression of the heart specimens from GDS651 validated that ALDOB, GAPDH, RPLP2, and IGK had good abilities to distinguish DCM from ICM. In addition, GSEA results showed that cell proliferation and differentiation were the hub biological processes related to ICM, while metabolic processes and cell signaling transduction were the hub biological processes associated with DCM.Conclusion: The present study identified five dysregulated hub circulating proteins among ICM patients and 19 dysregulated hub circulating proteins among DCM patients. Cell proliferation and differentiation were significantly enriched in ICM. Metabolic processes were strongly enhanced in DCM and may be used to distinguish DCM from ICM.Keywords: proteomics, ischemic cardiomyopathy, dilated cardiomyopathy, weighted gene co-expression network analysis, gene set enrichment analysis

Keywords

• proteomics
• ischemic cardiomyopathy
• dilated cardiomyopathy
• weighted gene co-expression network analysis
• gene set enrichment analysis