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

초록

Acute myocardial infarction (AMI) is a multifaceted syndromeinfluenced by the functions of various extrinsic and intrinsicpathways and pathological processes, which can be detectedin circulation using biomarkers. In this study, we investigatedthe secretome protein profile of induced-hypertrophy cardiomyocytesto identify next-generation biomarkers for AMI diagnosisand management. Hypertrophy was successfully induced inimmortalized human cardiomyocytes (T0445) by 200 nM ET-1and 1 μM Ang II. The protein profiles of hypertrophied cardiomyocytesecretomes were analyzed by nano-liquid chromatographywith tandem mass spectrometry and differentially expressedproteins that have been identified by Ingenuity PathwayAnalysis. The levels of 32 proteins increased significantly(＞1.4 fold), whereas 17 proteins (＜0.5 fold) showed a rapiddecrease in expression. Proteomic analysis showed significantupregulation of six 14-3-3 protein isoforms in hypertrophiedcardiomyocytes compared to those in control cells. Multi-reactionmonitoring results of human plasma samples showed that14-3-3 protein-zeta levels were significantly elevated in patientswith AMI compared to those of healthy controls. These findingselucidated the role of 14-3-3 protein-zeta in cardiac hypertrophyand cardiovascular disorders and demonstrated its potential asa novel biomarker and therapeutic strategy.

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