Yang Guodong, Chen Shuping, Ma Aiqun, Lu Jun, Wang Tingzhong
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.
Key Laboratory of Molecular Cardiology, Shaanxi Province, China.
Clinics (Sao Paulo). 2017 Oct;72(10):600-608. doi: 10.6061/clinics/2017(10)03.
Clinically, patients with chronic heart failure arising from different etiologies receive the same treatment. However, the prognoses of these patients differ. The purpose of this study was to elucidate whether the pathogenesis of heart failure arising from different etiologies differs.
Heart failure-related dataset GSE1145 was obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. A protein-protein interaction network of the differentially expressed genes was constructed using Search Tool for the Retrieval of Interacting Genes. The modules in each network were analyzed by Molecular Complex Detection of Cytoscape. The Database for Annotation, Visualization and Integrated Discovery was used to obtain the functions of the modules.
Samples contained in GSE1145 were myocardial tissues from patients with dilated cardiomyopathy, familial cardiomyopathy, hypertrophic cardiomyopathy, ischemic cardiomyopathy, and post-partum cardiomyopathy. The differentially expressed genes, modules, and functions of the modules associated with different etiologies varied. Abnormal formation of extracellular matrix was overlapping among five etiologies. The change in cytoskeleton organization was specifically detected in dilated cardiomyopathy. The activation of the Wnt receptor signaling pathway was limited to hypertrophic cardiomyopathy. The change in nucleosome and chromatin assembly was associated with only familial cardiomyopathy. Germ cell migration and disrupted cellular calcium ion homeostasis were solely detected in ischemic cardiomyopathy. The change in the metabolic process of glucose and triglyceride was detected in only post-partum cardiomyopathy.
These results indicate that the pathogenesis of heart failure arising from different etiologies varies, which may provide molecular evidence supporting etiology-based treatment for heart failure patients.
临床上，由不同病因引起的慢性心力衰竭患者接受相同的治疗。然而，这些患者的预后不同。本研究的目的是阐明不同病因引起的心力衰竭的发病机制是否不同。
从基因表达综合数据库中获取心力衰竭相关数据集GSE1145。使用R软件识别差异表达基因。使用检索相互作用基因的搜索工具构建差异表达基因的蛋白质-蛋白质相互作用网络。通过Cytoscape的分子复合物检测分析每个网络中的模块。使用注释、可视化和综合发现数据库获取模块的功能。
GSE1145中包含的样本是来自扩张型心肌病、家族性心肌病、肥厚型心肌病、缺血性心肌病和产后心肌病患者的心肌组织。与不同病因相关的差异表达基因、模块及其功能各不相同。细胞外基质的异常形成在五种病因中都有重叠。细胞骨架组织的变化在扩张型心肌病中被特异性检测到。Wnt受体信号通路的激活仅限于肥厚型心肌病。核小体和染色质组装的变化仅与家族性心肌病有关。生殖细胞迁移和细胞钙离子稳态破坏仅在缺血性心肌病中被检测到。葡萄糖和甘油三酯代谢过程的变化仅在产后心肌病中被检测到。
这些结果表明，不同病因引起的心力衰竭的发病机制各不相同，这可能为心力衰竭患者基于病因的治疗提供分子证据。
