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Updated: Oct 2, 2025
Mesoscopic Optical Imaging of Whole Mouse Heart
Published on: October 14, 2021
A multi-omics approach to identify molecular alterations in a mouse model of heart failure
Xiang Zhou1, Shuchen Zhang1, Yiheng Zhao1
1Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Insights
This study reveals key molecular changes in heart failure (HF) using multi-omics. Immune cell activation and altered gene regulation in endothelial cells offer new insights into pressure overload-induced HF.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Heart failure (HF) poses a growing global health burden with increasing morbidity and mortality.
- The precise molecular mechanisms underlying HF pathogenesis, particularly in response to pressure overload, require further elucidation.
Purpose of the Study:
- To investigate the molecular alterations contributing to pressure overload-induced heart failure (HF).
- To identify key cellular pathways and regulatory networks involved in HF development.
Main Methods:
- Generation of a pressure overload-induced HF mouse model via transverse aortic constriction.
- Comprehensive multi-omics analysis integrating single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq), bulk ATAC-seq, and miRNA sequencing.
- Validation of omics findings using immunofluorescence staining.
Main Results:
- Identification of five major cell types in the HF heart, consistent with prior research.
- Integrative omics analysis revealed significant alterations in gene expression, highlighting the role of immune response pathways.
- scATAC-seq data indicated dysregulated gene regulation related to nitric oxide (NO) biosynthesis in endothelial cells of failing hearts.
- Perturbed miRNA expression correlated with altered gene expression in immune cells, confirming their involvement in HF pathogenesis.
Conclusions:
- Multi-omics profiling provides mechanistic insights into pressure overload-induced heart failure.
- The study identifies specific molecular signatures, including immune cell activation and endothelial cell dysfunction, contributing to HF.
- This research offers a foundation for developing targeted therapeutic strategies for HF.
Abstract:
Rationale: The morbidity and mortality of heart failure (HF) have been increasing rapidly in recent years. However, the molecular events that link to the phenotype of HF remain unclear. This study aimed to investigate the molecular alterations in the pathogenesis of HF induced by pressure overload. Methods: Transverse aortic constriction was conducted to generate the HF mouse model. A multi-omics study was performed, including integrative analysis of scRNA-seq, scATAC-seq, bulk ATAC-seq and miRNA-seq data. The results of omics analysis were verified by immunofluorescence staining. Results: scRNA-seq analysis identified five major cell types, which exhibits consistency with previous studies. Integrative analysis of ATAC-seq and miRNA-seq showed the alterations of gene expression in HF. Activation of genes involved in immune response at transcriptional level and perturbed expression of their upstream miRNAs confirmed the function of immune cells in the pathogenesis of HF. Analysis of scATAC-seq revealed a NO biosynthetic related gene regulation pattern in endothelial cells of failing hearts. Conclusion: We performed a multi-omics analysis, comparing the transcriptomic, miRNA expression, and chromatin accessibility profile between the HF and control mice, thus providing mechanistic insights into the pathogenesis of pressure overload-induced HF.
