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Transcriptomic Signatures of End-Stage Human Dilated Cardiomyopathy Hearts with and without Left Ventricular Assist
Mihir Parikh1,2, Saumya Shah1,2, Ratnadeep Basu1,2
1Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
International Journal of Molecular Sciences
|February 26, 2022
Summary
Left ventricular assist device (LVAD) therapy impacts gene expression in dilated cardiomyopathy (DCM) patients. LVAD improves immune response and ventricular remodeling, but chamber-specific transcriptomic changes persist.
Area of Science:
- Cardiology
- Genomics
- Molecular Biology
Background:
- Dilated cardiomyopathy (DCM) presents complex ventricular dynamics.
- Right ventricular (RV) failure is a significant complication after left ventricular assist device (LVAD) implantation.
- Understanding transcriptomic changes in DCM and post-LVAD is crucial for improving outcomes.
Purpose of the Study:
- To investigate transcriptomic signatures in end-stage DCM.
- To evaluate changes in gene (mRNA) and microRNA (miRNA) expression following LVAD implantation.
- To elucidate chamber-specific transcriptomic alterations in response to LVAD.
Main Methods:
- Collected LV and RV free-wall tissues from DCM patients with and without LVAD, and from non-failing controls.
- Utilized microarrays to determine mRNA and miRNA expression levels.
- Analyzed enriched pathways and differentially expressed genes/miRNAs.
Main Results:
- End-stage DCM hearts showed enriched pathways related to immune response, oxygen homeostasis, and cellular processes in both ventricles.
- LV genes involved in circadian rhythm, muscle contraction, hypertrophy, and ECM remodeling were differentially expressed.
- LVAD improved immune response genes in both ventricles, normalized oxygen homeostasis and ECM remodeling genes in the LV, and normalized four miRNAs.
Conclusions:
- LVAD therapy induces transcriptomic changes in mRNAs and miRNAs, contributing to reverse ventricular remodeling.
- These transcriptomic modifications occur in a chamber-specific manner.
- LVAD influences immune response, oxygen homeostasis, and ECM remodeling pathways, impacting ventricular function post-implantation.
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