Construction of a murine model of pathological cardiac remodeling and transcriptomic analysis

doi:10.16352/j.issn.1001-6325.2026.10.1322

Abstract

Abstract: Objective Mouse myocardial transcriptome sequencing data were analyzed to identify transcription factors regulating pathological cardiac remodeling,and to elucidate its mechanism. Methods A mouse cardiac remodeling 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 significantly 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 extracellular matrix(ECM) receptor pathway was markedly activated,and Etv4 expression in myocardial tissue showed a significant 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.

Key words: transcription factor Etv4, extracellular matrix receptor interaction pathway, pathological myocardial remodelling

CLC Number:

LIU Ruyi, DENG Hui, ZHANG Shu, YANG Xiaowen, DONG Daqian, LIU Tianlong, ZHENG Wei. Construction of a murine model of pathological cardiac remodeling and transcriptomic analysis[J]. Basic & Clinical Medicine, 2026, 46(10): 1322-1328.

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