Analysis of Gene Expression During the Development of Congestive Heart Failure After Myocardial Infarction in Rat Models

Abstract

SummaryOur study aimed to investigate the gene expression at different myocardial infarction (MI) phases and to understand the development mechanisms of congestive heart failure (CHF) after MI. Dataset GSE1957 including 24 samples of rat left ventricles at 1-day post MI or sham operation and 7-day post MI or sham operation was downloaded from Gene Expression Ominibus. The data were normalized with an affyPLM package and differentially expressed genes (DEGs) were identified with a Linear Models for Microarray Data package. Heat maps of the DEGs were constructed using Cluster 3.0. GO (Gene Ontology) enrichment analysis of the DEGs was performed in Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed by Biomolecular Interaction Network Database and visualized by Cytoscape, and a subnetwork was analyzed using plugin ClusterONE in Cytoscape. A total of 5 DEGs at 1-day post-MI, 5 DEGs at 7-day post-MI, and 7 DEGs between the MI and sham groups at 1-day and 7-day post-MI were identified. For the GO category analysis, DEGs at 1-day post-MI were enriched in response to cytokine stimulus. DEGs at 7-day post-MI were enriched in response to inorganic substance and chemical homeostasis. DEGs between 1-day and 7-day post-MI including CDK2 and CDC20 were significantly enriched in mitosis. CDK2, ANXA1, CDC20, and AQP2 were included in the PPI network, and CDK2 was the only DEG included in the subnetwork. In conclusion, the induction of DEGs at 7-day post-MI might participate in the response to a hormone and endogenous stimulus to regulate the development of CHF after MI. (Int Heart J 2015; 56: 444-449) Key words: Differentially expressed gene, Interaction network, CDK2, AQP2 M yocardial infarction (MI) is commonly known as heart attack. MI is a leading cause of heart failure and one of the major causes of the death and disability, and is a chronic disease and can even go undetected, eventually leading to a sudden death.1,2) Patients with MI sometimes have chest pain while 64% of the cases may not even have any symptoms.3) Therefore, an urgent task is to develop diagnostic and therapeutic methods for MI.In recent years, studies on genes have provided us with information for disease diagnosis and therapy due to their high sensitivity, specificity, and fast speed. The relation between gene expression and MI has been studied extensively, and the progression of congestive heart failure (CHF) after MI is complex and related to several changes. [4][5][6][7] For example, the variants of gene ALOX5AP which encodes 5-lipoxygenase activating protein are associated with the pathogenesis of MI by increasing leukotriene production and inflammation. 4) Andersson, et al reported that the expression of 10 neuronal type regulated genes including muscarinic m4, ATP receptor P2rx4, nerve growth factor receptor, and cardiac Kcne1 were all increased in 7-day post-MI CHF hearts, while fewer genes were differentially expressed at 1-day post MI. 6) However, the underlying funct...

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Natriuretic Peptide Processing in Patients with and Without Left Ventricular Dysfunction

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