PPAR 相关基因在慢性心力衰竭中的作用：来自大样本的证据。

Role of PPAR-related genes in chronic heart failure: evidence from large populations.

机构信息

Department of Geriatrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.

Department of Cardiology, Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, 200040, China.

出版信息

BMC Cardiovasc Disord. 2023 Nov 10;23(1):552. doi: 10.1186/s12872-023-03554-8.

DOI:10.1186/s12872-023-03554-8

PMID:37950149

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10638691/

Abstract

BACKGROUND

The role of PPAR signaling and its associated genes in the pathogenesis and progression of chronic heart failure (CHF) remains elusive.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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

过氧化物酶体增殖物激活受体（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不清楚。

方法

我们从基因表达综合数据库（GEO）中获取了 CHF 样本的基因表达谱和相关基线信息，具体来自于 GSE57338 项目。

结果

从 GSE57338 项目中，我们得到了 126 个与 PPAR 相关的基因的表达值。然后建立了一个蛋白质-蛋白质相互作用网络来阐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、脂质代谢过程的调节、脂肪酸代谢、循环系统血管过程、酒精代谢、甘油三酯代谢以及脂质定位和对营养物质的反应的调节等功能。我们使用 Cytoscape 中的 cytohubba 插件，确定了 ACADM、PPARG 和 CPT2 作为 HF 发病和进展中潜在的核心分子。随后的基因本体论和京都基因与基因组百科全书分析深入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，这些基因可能显著影响中性粒细胞和 M2 巨噬细胞的浸润水平，从而在 CHF 机制中发挥作用。