Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Proteome-wide Characterization and Pathophysiology Correlation in Non-ischemic Cardiomyopathies

  • Seonhwa Lee (Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Keimyung University School of Medicine) ;
  • Dong-Gi Jang (Center for RNA Research, Institute for Basic Science) ;
  • Yeon Ju Kyoung (Center for RNA Research, Institute for Basic Science) ;
  • Jeesoo Kim (Center for RNA Research, Institute for Basic Science) ;
  • Eui-Soon Kim (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology) ;
  • Ilseon Hwang (Department of Pathology, Keimyung University Dongsan Hospital, Keimyung University School of Medicine) ;
  • Jong-Chan Youn (Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea) ;
  • Jong-Seo Kim (Center for RNA Research, Institute for Basic Science) ;
  • In-Cheol Kim (Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Keimyung University School of Medicine)
  • Received : 2024.01.23
  • Accepted : 2024.05.08
  • Published : 2024.08.01
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Abstract

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF-2020R1C1C1014161 to Kim IC, NRF-2021R1F1A1063430 to Youn JC), and Comparative Medicine Disease Research Center (NRF-2021R1A5A1033157 to Kim JS); by the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI22C0198) to Kim IC; by the fund from the Korean Cardiac Research Foundation (202202-01) and by the Research Fund of Seoul St. Mary's Hospital, Catholic University of Korea (2022) to Youn JC. Kim JS thanks the Institute for Basic Science (IBS-R008-D1), funded by the Ministry of Science and ICT of Korea, for support.

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