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Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice
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Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers.
S W Tobin1,2,3, S Hashemi1,2,3, K Dadson1
1Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
Scientific Reports
|July 2, 2017
Summary
Myocyte Enhancer Factor 2 (MEF2) activity in heart failure (HF) was investigated. Beta-blocker treatment improved cardiac function and altered MEF2-regulated gene networks, revealing potential therapeutic targets for HF.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Genomics
Background:
- Myocyte Enhancer Factor 2 (MEF2) plays a key role in cardiac remodeling during heart failure (HF).
- Beta-adrenergic signaling, a primary HF treatment, targets MEF2.
- Understanding MEF2-mediated gene networks in HF is crucial for therapeutic development.
Purpose of the Study:
- To identify global gene transcription networks regulated by MEF2 in heart failure.
- To investigate the impact of beta-blocker treatment on these networks.
- To uncover novel MEF2 target genes with potential diagnostic or therapeutic value in HF.
Main Methods:
- Experimental heart failure induced by transverse aortic constriction (TAC) in mice.
- Treatment with Atenolol (a beta-blocker) or solvent control.
- Transcriptome analysis using RNA-sequencing on left ventricular samples and MEF2A-depleted cardiomyocytes.
Main Results:
- Atenolol treatment improved cardiac function in TAC mice and repressed MEF2 activity.
- TAC induced 65 differentially expressed genes (DEGs) related to inflammation, cell migration, and apoptosis.
- Atenolol reversed the expression of 28 of these TAC-mediated DEGs.
- Rarres2 was identified as a novel MEF2 target gene upregulated in HF and responsive to isoproterenol.
Conclusions:
- MEF2 activity and its downstream gene networks are significantly altered in heart failure.
- Beta-blocker therapy modulates these networks, offering therapeutic benefits.
- Identified genes, including Rarres2, represent potential targets for heart failure diagnosis and treatment.
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