病理性心肌重构小鼠模型的构建及转录组测序分析OA

Objective Mouse myocardial transcriptome sequencing data were analyzed to identify transcription fac-tors regulating pathological cardiac remodeling,and to elucidate its mechanism.Methods A mouse cardiac remode-ling model was established via subcutaneous implantation of angiotensin Ⅱ(AngⅡ)micro-osmotic pump,and the mouse model was evaluated at anatomical and pathological levels.Transcriptomic sequencing of mouse myocardial tissue was performed to identify differentially expressed transcription factors between groups.Gene Set Enrichment Analysis(GSEA)was employed to delineate relevant signalling pathways.Pearson correlation analysis was used to establish correlations between transcription factors and signalling pathways,which were validated by western blot.Results After micro-osmosis pump implantation for 4 weeks,significant alterations in cardiac structure and function were observed.Compared with control mice,the mice in model group exhibited markedly reduced ejection fraction(EF)and shortening fraction(FS)(P＜0.05),while heart-to-tibia weight ratio and heart-to-leg ratio were signifi-cantly increased in the model group mice(P＜0.05).The myocardial WGA staining and Picro Sirius Red staining of myocardial tissue revealed that the mouse heart in model group exhibited significant increased in cardiac hypertrophy and fibrosis(P＜0.05).Transcriptomic sequencing data revealed a significantly increase in transcription factor Etv4 expression in mouse myocardial tissue from the model mice compared with vehicle mice.The extracellu-lar matrix(ECM)receptor pathway was markedly activated,and Etv4 expression in myocardial tissue showed a sig-nificant positive correlation with gene expression involved in the ECM receptor pathway(P＜0.05),which was further validated at the protein level.Conclusions The transcription factors Etv4 may facilitate pathological cardiac remodeling,potentially via the ECM receptor pathway.