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Discovery of 14-3-3 zeta as a potential biomarker for cardiac hypertrophy

  • Joyeta Mahmud (Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology) ;
  • Hien Thi My Ong (Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology) ;
  • Eda Ates (Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology) ;
  • Hong Seog Seo (Cardiovascular Center, Korea University Guro Hospital, Korea University Medicine) ;
  • Min-Jung Kang (Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology)
  • Received : 2022.11.24
  • Accepted : 2023.03.24
  • Published : 2023.06.30

Abstract

Acute myocardial infarction (AMI) is a multifaceted syndrome influenced by the functions of various extrinsic and intrinsic pathways and pathological processes, which can be detected in circulation using biomarkers. In this study, we investigated the secretome protein profile of induced-hypertrophy cardiomyocytes to identify next-generation biomarkers for AMI diagnosis and management. Hypertrophy was successfully induced in immortalized human cardiomyocytes (T0445) by 200 nM ET-1 and 1 μM Ang II. The protein profiles of hypertrophied cardiomyocyte secretomes were analyzed by nano-liquid chromatography with tandem mass spectrometry and differentially expressed proteins that have been identified by Ingenuity Pathway Analysis. The levels of 32 proteins increased significantly (>1.4 fold), whereas 17 proteins (<0.5 fold) showed a rapid decrease in expression. Proteomic analysis showed significant upregulation of six 14-3-3 protein isoforms in hypertrophied cardiomyocytes compared to those in control cells. Multi-reaction monitoring results of human plasma samples showed that 14-3-3 protein-zeta levels were significantly elevated in patients with AMI compared to those of healthy controls. These findings elucidated the role of 14-3-3 protein-zeta in cardiac hypertrophy and cardiovascular disorders and demonstrated its potential as a novel biomarker and therapeutic strategy.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT, Republic of Korea (no. NRF-2017R1A2B2004398, NRF-2021R1A2C209370611), and the Korea Institute of Science and Technology (KIST) Institutional Program (2E31623).

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