RNA sequencing and gene network analysis identified troponin T type 1 (Tnnt1) as the core gene regulating 31 neighboring genes in a mouse model of HFpEF.
RNA sequencing in a mouse model of HFpEF identified Tnnt1 as a core gene in the disease's development, providing a potential novel therapeutic target.
INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality but without available evidence-based therapies. It is essential to investigate changes in gene expression profiles in preclinical HFpEF animal models, with the aim of searching for novel therapeutic targets. METHODS: Wild-type male C57BL/6J mice were administrated with a combination of high-fat diet (HFD) and inhibition of constitutive nitric oxide synthase using N-nitro-l-arginine methyl ester (l-NAME) for 5 and 7 weeks. RNA sequencing was conducted to detect gene expression profiles, and bioinformatic analysis was performed to identify the core genes, pathways, and biological processes involved. RESULTS: A total of 1,347 genes were differentially expressed in the heart at week 5 and 7 post-intervention. Gene Ontology enrichment analysis indicated that these greatly changed genes were involved mainly in cell adhesion, neutrophil chemotaxis, cell communication, and other functions. Using hierarchical cluster analysis, these differentially expressed genes were classified into 16 profiles. Of these, three significant profiles were ultimately identified. Gene co-expression network analysis suggested troponin T type 1 (Tnnt1) directly regulated 31 neighboring genes and was considered to be at the core of the associated gene network. CONCLUSION: The combined application of RNA sequencing, hierarchical cluster analysis, and gene network analysis identified Tnnt1 as the most important gene in the development of HFpEF.
Sun et al. (Mon,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). High-fat diet (HFD) and N-nitro-l-arginine methyl ester (l-NAME) was evaluated on Differentially expressed genes. RNA sequencing and gene network analysis identified troponin T type 1 (Tnnt1) as the core gene regulating 31 neighboring genes in a mouse model of HFpEF.