关键词: Bioinformatics Biological Heart Failure Microenvironment PPAR

Mesh : Humans Gene Expression Profiling / methods PPAR gamma Protein Interaction Maps / genetics Heart Failure / diagnosis genetics Lipids Computational Biology / methods

来  源:   DOI:10.1186/s12872-023-03554-8   PDF(Pubmed)

Abstract:
The role of PPAR signaling and its associated genes in the pathogenesis and progression of chronic heart failure (CHF) remains elusive.
We accessed the gene expression profile and relevant baseline information of CHF samples from the Gene Expression Omnibus (GEO) database, specifically from the GSE57338 project.
From GSE57338 project, we derived the expression value of 126 PPAR-related genes. A protein-protein interaction network was then established to illustrate potential protein interactions. ClueGO analysis results revealed that these genes predominantly participate in functions such as export across plasma membrane, regulation of lipid metabolic process, fatty acid metabolism, circulatory system vascular processes, alcohol metabolism, triglyceride metabolism and regulation of lipid localization and response to nutrient. Using the cytohubba plug-in in Cytoscape, we pinpointed ACADM, PPARG and CPT2 as potential central molecules in HF pathogenesis and progression. Subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis delved into the potential biological role of these three genes in CHF. Immune infiltration analysis suggested that the infiltration level of neutrophils and M2 macrophages might be notably influenced by these genes, thereby playing a role in the CHF mechanism.
Our research provides a comprehensive insight into the significance of PPAR associated genes in CHF development. Notably, the genes ACADM, PPARG and CPT2 emerged as potential targets for clinical interventions.
摘要:
背景:PPAR信号及其相关基因在慢性心力衰竭(CHF)的发病机制和进展中的作用仍然难以捉摸。
方法:我们从基因表达综合(GEO)数据库获取了CHF样本的基因表达谱和相关基线信息,具体来自GSE57338项目。
结果:来自GSE57338项目,我们得出了126个PPAR相关基因的表达值。然后建立蛋白质-蛋白质相互作用网络以说明潜在的蛋白质相互作用。ClueGO分析结果表明,这些基因主要参与跨质膜输出等功能,调节脂质代谢过程,脂肪酸代谢,循环系统血管过程,酒精代谢,甘油三酯代谢和调节脂质定位和对营养的反应。使用Cytoscape中的cytohubba插件,我们确定了ACADM,PPARG和CPT2作为HF发病机制和进展中的潜在中枢分子。随后的基因本体论和京都百科全书的基因和基因组分析探讨了这三个基因在CHF中的潜在生物学作用。免疫浸润分析表明,中性粒细胞和M2巨噬细胞的浸润水平可能受到这些基因的显著影响,从而在CHF机制中发挥作用。
结论:我们的研究为PPAR相关基因在CHF发展中的意义提供了全面的见解。值得注意的是,基因ACADM,PPARG和CPT2成为临床干预的潜在目标。
公众号