Effect of left ventricular assist device on myocardial transcriptome of cardiomyopathy
Objective To investigate the effect of left ventricular assist device(LVAD)on myocardial gene expression profile in patients with end-stage cardiomyopathy and its biological significance.Methods Myocardial mRNA expression profile data set of patients with end-stage heart failure with reduced ejection fraction implanted with LVAD was retrieved and screened from the GEO database(http://www.ncbi.nlm.nih.gov/geo).The common differentially expressed genes(DEG)of target data set were screened by Venn diagram,and DEG from at least two data sets were selected for subsequent analysis.The DEG was screened by GEO2R and verified by GSE52601.Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene set enrichment analysis(GSEA)were performed on DEG.STRING and Cytoscape were used to construct protein-protein interaction networks to identify core modules and hubgenes.Results A total of 4 target data sets GSE430,GSE974,GSE21610 and GSE52601 were retrieved.The GSE430,GSE974,GSE21610 were used as training sets and GSE52601 as verification set to verify the selected core DEG.A total of 33 DEG(22 down-regulated and 11 up-regulated)were identified,which were related to neutrophil degranulation and G protein-coupled receptor ligand binding.A core module composed of 15 hub genes was screened out,which was related to the response and regulation of inflammatory injury and chemokine signal transduction mediated by G protein-coupled receptors,and involved in pathways such as mitogen-activated protein(MAP)/extracellular signal-regulated ki-nase(ERK),actin filament,gamma-aminobutyric acid β(GABA-B)receptor,sialic acid,prostaglandin E receptor,CD40 receptor and interleukin-8 receptor.Plasminogen activator urokinase gene(PLAU)and CD163 molecular genes showed the same trend in validation set.Conclusion It is demonstrated that molecular mechanism of LVAD on myocardial pathological remodeling is re-lated to inflammatory pathway mediated by G protein-coupled receptor,which provides genetic basis for selecting appropriate type of LVAD and evaluating therapeutic effect of LVAD.
NETL
NSTL
万方数据
