Abstract Body: Common Genes Related to Metabolism of Physiological and Pathological Cardiac Hypertrophy

Xiaojian Cai¹, Liling Zheng ^1*, Shuping Zhong^1,2*#
1, First Hospital of Quanzhou Affiliated to Fujian Medical University.
2. Keck School of Medicine, University of Southern California.
Physiological and pathological cardiac hypertrophy exhibit markedly different phenotypes and underlying molecular mechanisms such as metabolic reprogramming. We have explored key metabolism-associated genes which are commonly involved in physiological and pathological cardiac hypertrophy, seeking shared metabolic nodes that might underline hypertrophic growth. We have applied cardiac hypertrophy-related transcriptomic data (GSE776) from the NCBI GEO database to retrieve metabolism-associated genes in MSigDB database. Differentially expressed genes (DEGs) in physiological (exercise-induced) and pathological (high-salt diet-induced) hypertrophy models were screened and intersected with metabolic gene sets to identify candidate targets. Functional validation of candidate genes has been performed in vivo using mouse models, such as pregnancy-induced physiological hypertrophy and isoproterenol-induced pathological hypertrophy. Additionally, in vitro validation have been conducted in isoproterenol-treated neonatal rat cardiomyocytes. Transcriptomic analysis of the GSE776 dataset have revealed four metabolism-associated genes (HSD17B4, PGM1, PPM1B and HAND2) consistently upregulated in both physiological and pathological cardiac hypertrophy. These genes are involved in key pathways including fatty acid oxidation, glucose metabolism, stress response, and transcriptional regulation. In vivo and in vitro experiments have confirmed the significant upregulation of these four genes in hypertrophic myocardial tissues and cardiomyocytes. Immunohistochemical staining of human myocardial tissues has furthermore confirmed that all four genes are upregulated in hypertrophic myocardium compared to non-hypertrophic myocardium. This study have identified four key metabolism-associated genes involved in physiological and pathological cardiac hypertrophy, providing new insights into the shared metabolic remodeling underlying cardiac hypertrophy and highlighting potential novel targets for further mechanistic and translational investigation.
*: Corresponding authors; #: Professor Emeritus, University of Southern California.