Abstract：
BACKGROUND: 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.
CONCLUSIONS: 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.
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-
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.
CONCLUSIONS: 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.
摘要：
背景：射血分数保留的心力衰竭（HFpEF）是一种常见综合征，具有高发病率和高死亡率，但没有可用的循证疗法。研究临床前HFpEF动物模型中基因表达谱的变化至关重要。目的是寻找新的治疗靶点。
方法：野生型雄性C57BL/6J小鼠给予高脂饮食（HFD）和使用N-硝基-l -精氨酸甲酯（l -NAME）抑制组成型一氧化氮合酶的组合，持续5周和7周。进行RNA测序以检测基因表达谱，并进行生物信息学分析以鉴定核心基因，通路,和涉及的生物过程。
结果：在干预后第5周和第7周，共有1,347个基因在心脏中差异表达。基因本体论富集分析表明,这些发生较大改变的基因主要参与细胞粘附,中性粒细胞趋化性，细胞通讯，和其他功能。使用层次聚类分析，这些差异表达的基因分为16个。其中,最终确定了三个重要的概况.基因共表达网络分析表明，肌钙蛋白T1型（Tnnt1）直接调节31个相邻基因，被认为是相关基因网络的核心。
结论：RNA测序的联合应用，层次聚类分析，和基因网络分析确定Tnnt1是HFpEF发展中最重要的基因。
方法：野生型雄性C57BL/6J小鼠给予高脂饮食（HFD）和使用N-硝基-
结果：在干预后第5周和第7周，共有1,347个基因在心脏中差异表达。基因本体论富集分析表明,这些发生较大改变的基因主要参与细胞粘附,中性粒细胞趋化性，细胞通讯，和其他功能。使用层次聚类分析，这些差异表达的基因分为16个。其中,最终确定了三个重要的概况.基因共表达网络分析表明，肌钙蛋白T1型（Tnnt1）直接调节31个相邻基因，被认为是相关基因网络的核心。
结论：RNA测序的联合应用，层次聚类分析，和基因网络分析确定Tnnt1是HFpEF发展中最重要的基因。
