Zhou Guofeng, Sun Shaoyan, Yuan Qiuyue, Zhang Run, Jiang Ping, Li Guangyu, Wang Yong, Li Xiao
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
School of Mathematics and Statistics, Ludong University, Yantai, China.
Front Genet. 2021 Jul 8;12:668702. doi: 10.3389/fgene.2021.668702. eCollection 2021.
Heart failure with preserved ejection fraction (HFpEF) is a complex disease characterized by dysfunctions in the heart, adipose tissue, and cerebral arteries. The elucidation of the interactions between these three tissues in HFpEF will improve our understanding of the mechanism of HFpEF. In this study, we propose a multilevel comparative framework based on differentially expressed genes (DEGs) and differentially correlated gene pairs (DCGs) to investigate the shared and unique pathological features among the three tissues in HFpEF. At the network level, functional enrichment analysis revealed that the networks of the heart, adipose tissue, and cerebral arteries were enriched in the cell cycle and immune response. The networks of the heart and adipose tissues were enriched in hemostasis, G-protein coupled receptor (GPCR) ligand, and cancer-related pathway. The heart-specific networks were enriched in the inflammatory response and cardiac hypertrophy, while the adipose-tissue-specific networks were enriched in the response to peptides and regulation of cell adhesion. The cerebral-artery-specific networks were enriched in gene expression (transcription). At the module and gene levels, 5 housekeeping DEGs, 2 housekeeping DCGs, 6 modules of merged protein-protein interaction network, 5 tissue-specific hub genes, and 20 shared hub genes were identified through comparative analysis of tissue pairs. Furthermore, the therapeutic drugs for HFpEF-targeting these genes were examined using molecular docking. The combination of multitissue and multilevel comparative frameworks is a potential strategy for the discovery of effective therapy and personalized medicine for HFpEF.
射血分数保留的心力衰竭（HFpEF）是一种复杂的疾病，其特征是心脏、脂肪组织和脑动脉功能失调。阐明HFpEF中这三种组织之间的相互作用将增进我们对HFpEF发病机制的理解。在本研究中，我们基于差异表达基因（DEG）和差异相关基因对（DCG）提出了一个多层次比较框架，以研究HFpEF中三种组织之间共同的和独特的病理特征。在网络层面，功能富集分析表明，心脏、脂肪组织和脑动脉的网络在细胞周期和免疫反应方面富集。心脏和脂肪组织的网络在止血、G蛋白偶联受体（GPCR）配体和癌症相关途径方面富集。心脏特异性网络在炎症反应和心肌肥大方面富集，而脂肪组织特异性网络在对肽的反应和细胞黏附调节方面富集。脑动脉特异性网络在基因表达（转录）方面富集。在模块和基因层面，通过组织对的比较分析鉴定出5个管家DEG、2个管家DCG、6个合并的蛋白质-蛋白质相互作用网络模块、5个组织特异性枢纽基因和20个共享枢纽基因。此外，使用分子对接研究了针对这些基因的HFpEF治疗药物。多组织和多层次比较框架的结合是发现HFpEF有效治疗方法和个性化药物的潜在策略。
