Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, Hebei 061000, P.R. China.
Mol Med Rep. 2018 Aug;18(2):1955-1962. doi: 10.3892/mmr.2018.9161. Epub 2018 Jun 14.
Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia‑reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene co‑expression network analysis, hierarchical clustering, protein‑protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene co‑expression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC proto‑oncogene, non‑receptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.
急性心肌梗死可引起心室重构,从而导致心脏扩张和心力衰竭。心肌重构的发病机制尚不清楚。本研究旨在鉴定缺血再灌注(IR)后心肌重构的关键基因和网络。首先,从国家生物技术信息中心数据库下载 mRNA 表达数据,以鉴定 IR 心脏在第 2 天和第 7 天的 mRNA 表达差异。然后,采用加权基因共表达网络分析、层次聚类、蛋白质-蛋白质相互作用(PPI)网络、基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路,鉴定 IR 后心脏重构过程中的关键基因和网络。在心脏重构过程中鉴定出 3321 个差异表达基因。通过基因共表达网络分析共鉴定出 6 个模块。GO 和 KEGG 分析结果表明,每个模块代表不同的生物学功能,与不同的途径相关。最后,通过 PPI 网络构建鉴定每个模块的枢纽基因。本研究表明,IR 后心脏重构是一个复杂的过程,涉及细胞外基质组织、神经发育、细胞凋亡和能量代谢。失调基因,包括 SRC 原癌基因、非受体酪氨酸激酶、Discs large MAGUK 支架蛋白 1、三磷酸柠檬酸裂解酶、RAN、RAS 癌基因家族成员、肿瘤蛋白 p53 和 polo 样激酶 2,可能对 IR 后心脏重构至关重要,并可能作为急性心肌梗死后抑制心脏重构的潜在靶点。