Characterization of Myocardial Proteomics in Biopsy Proven Cardiomyopathies

Abstract Background Difference in proteomic expression according to the etiology of cardiomyopathies is not well known. Purpose We aimed to identify proteome based pathogenesis in patients with biopsy proven cardiomyopathies. Methods Comparative proteomic analysis of biopsy specimens were performed from 9 patients with cardiomyopathy (3 dilated cardiomyopathy (DCM), 2 hypertrophic cardiomyopathy (HCM) and 4 myocarditis) as well as 5 controls (normal endomyocardial biopsy specimen from one-year surveillance of heart transplant recipients) by tandem mass tag combined with liquid chromatography-mass spectrometry. Differential expression protein analysis, gene ontology analysis and Ingenuity pathway analysis were done to discover molecular mechanism for the differentially expressed proteins in each cardiomyopathy compared to the control. Results Differential expression protein analysis showed higher proportion of significantly increased proteins (Log2 fold change ≥1) in HCM and myocarditis, whereas higher proportion of significantly decreased proteins (Log2 fold change ≤−1) in DCM compared to controls (Figure). According to the gene ontology analysis, upregulation of neutrophil degranulation, and down-regulation of mitochondrial translation protein was noted in patients with DCM. In patients with HCM, platelet degranulation protein was increased, and mitochondrial ATP synthesis coupled electron transport, was decreased. In patients with myocarditis, neutrophil related proteins and calcium ion binding protein was increased, but muscle cell development, protein was decreased. Ingenuity pathway analysis revealed downregulation of oxidative phosphorylation and upregulation of sirtuin signalling pathway both in DCM and HCM. In myocarditis, various pathways related to inflammation were upregulated with only RHO GDP dissociation inhibitors downregulated. Conclusions This study showed that each cardiomyopathy exhibited different proteomic expression compared to normal heart. Further large detailed study is needed to understand the association between proteomic expression and disease pathophysiology. Funding Acknowledgement Type of funding sources: None.