Screening And Identification Of Genes Closely Related To Myocardial Hypertrophy In Mice

ObjectiveCardiac hypertrophy is a common pathological process caused by cardiovascular diseases(such as hypertension and myocardial infarction),and is the main cause of heart failure and sudden death.However,the relevant factors in the occurrence and development of cardiac hypertrophy are not completely clear.This study combined bioinformatics analysis with biological experiments to screen and identify the key genes closely related to cardiac hypertrophy,laying a foundation for further exploration and analysis of the molecular mechanism of cardiac hypertrophy.MethodsWe downloaded the dataset GSE47420 from the national center for biotechnology information(National Center for Biotechnology Information,NCBI)GEO database(https://www.ncbi.nlm.nih.gov/geo/).We used data samples from wild type mice,including control group and Ang II group.Each group contained 3 C57Bl/6J mice sample and 3 Balb/C mice sample,respectively.On the basis of the GPL6887 platform(Illumina MouseWG-6 v2.0 expression beadchip),we used the GEO2 R online tool to screen the differentially expressed genes between C57Bl/6J and Balb/C control group and Ang II group with P <0.05 and |logFC|>0.5 as the threshold.The online database of DAVID6.7(https://davidd-d.ncifcrf.gov/)was used to carry out the gene ontology GO and signal pathway KEGG enrichment analysis of the co-differentially expressed genes in the two mice.On the basis of String database and Cytoscape software,we analyzed and visualized the protein interaction network of different genes and determined the hub gene by degree>10.By continuous pumping of Ang II,we established a model of cardiac hypertrophy in Kunming mice.The model was identified by ultrasound doppler,morphology and histology,and the expression of DEGS in cardiac hypertrophy was detected by qPCR.ResultsAfter analysis,202 common differentially expressed genes were obtained,including 127 up-regulated genes and 75 down-regulated genes.GO enrichment results showed that up-regulated genes were mainly enriched in collagen fibril organization,cellular response to mechanical stimulus,angiogenesis and other biological processes.The down-regulated genes were mainly enriched in metabolic process,oxidation-reduction process,fatty acid β-oxidation and other biological processes.The results of KEGG signaling pathway showed that up-regulated genes were mainly involved in proteoglycans in cancer and HIF-1 signaling pathway.Down-regulated genes were mainly involved in metabolic pathways,valine,leucine and isoleucine degradation and other signaling pathways.PPI analysis yielded 12 hub genes,including Dcn、Hadha、Col5a1、Hsp90aa1、Lox、Fbn1、Col3a1、Igf1、Loxl1、 Mmp2、Bgn and Timp1.qPCR results showed that the expression levels of hub genes Dcn、Hadha and Hsp90aa1 in hypertrophic myocardial tissue were significantly down-regulated.ConclusionsThis study screened and identified several genes and related signaling pathways with abnormal changes in the hypertrophic myocardium,which provided a new direction and experimental basis for the subsequent analysis of the molecular mechanism of the occurrence and development of cardiac hypertrophy.