Comprehensive Proteomic profiling and identification of 14-3-3 protein zeta as a potential diagnostic biomarker for Acute Myocardial Infarction

Abstract

Acute myocardial infarction (AMI) is a multifaceted syndrome influenced by the functions of various extrinsic and intrinsic pathological processes, which is also the leading cause of most cardiac death worldwide. This study aims to investigate the secretome protein profile of induced-hypertrophy cardiomyocytes to identify next-generation biomarkers for AMI diagnosis and management. Hypertrophy was induced successfully for immortalized human cardiomyocytes (T0445) by 200 nM ET-1 and 1 ？M Ang II. The protein profile of hypertrophied cardiomyocyte secretomes was analyzed by nano LC-MS/MS and differentially expressed proteins that have been investigated by Ingenuity Pathway Analysis. Our data reported a significant elevate of 32 proteins (>1.4 fold) while there are 17 proteins (<0.5 fold) showed a rapid decrease in expression. Proteomic analysis obtained a significant upregulation of six 14-3-3 protein isoforms in the secretome of hypertrophied cardiomyocytes compared to those in control cells and different cell types, including MKN-1, HFE-145, Hep-3B, Hepa-RG, A549, and L132. Label-free quantitative analysis of plasma from AMI patients revealed a significant upregulation of 14-3-3 zeta protein compared to healthy control samples. These findings elucidated the role of 14-3-3 zeta in cardiac hypertrophy and cardiovascular disorders and demonstrated its potential as a novel potential biomarker and therapeutic strategy.