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Updated: May 7, 2026
Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
Published on: September 15, 2018
MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy patients with MYBPC3 mutations
Diederik W D Kuster1, Joyce Mulders, Folkert J Ten Cate
1Dept. of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Cell and Molecular Physiology, Loyola University of Chicago, Maywood, IL, USA.
Insights
MicroRNAs (miRNAs) show altered expression in hypertrophic cardiomyopathy (HCM) patients with MYBPC3 mutations. These changes in cardiac myosin binding protein C-related HCM may impact cardiac signaling pathways.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biochemistry
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease often caused by mutations in sarcomeric protein genes.
- MYBPC3 mutations are a frequent cause of HCM, but the underlying disease mechanisms and clinical outcomes remain unclear.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases.
Purpose of the Study:
- To investigate the role of miRNAs in the pathogenesis of HCM caused by MYBPC3 mutations.
- To identify differentially expressed miRNAs in HCM patient hearts compared to healthy donor hearts.
- To explore the potential downstream effects of these miRNAs on cardiac gene expression and signaling.
Main Methods:
- miRNA arrays were performed on heart tissue from HCM patients (MYBPC3 mutation) and non-failing donors.
- Differential miRNA expression analysis was conducted using stringent statistical criteria (p<0.01, fold change ≥ 2).
- RT-PCR was used to validate miRNA expression and assess TRPM3 gene expression. In silico analysis identified potential mRNA targets.
Main Results:
- 13 miRNAs were found to be differentially expressed between HCM and donor hearts.
- miR-204, located within the TRPM3 gene locus, showed increased expression in HCM.
- A trend towards TRPM3 upregulation was observed in HCM myocardium.
- In silico analysis predicted that differentially expressed miRNAs target genes involved in cardiac hypertrophy and beta-adrenergic signaling.
- Reduced phosphorylation of cardiac troponin I was observed in HCM hearts.
Conclusions:
- HCM patients with MYBPC3 mutations exhibit a distinct miRNA expression profile.
- The identified miRNAs and their predicted mRNA targets suggest a role in aberrant cardiac signaling pathways in HCM.
- These findings contribute to understanding the molecular basis of HCM and may offer potential therapeutic targets.
Abstract:
Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in genes encoding sarcomeric proteins. One of the most frequent affected genes is MYBPC3, which encodes the thick filament protein cardiac myosin binding protein C. Despite the prevalence of HCM, disease pathology and clinical outcome of sarcomeric mutations are largely unknown. We hypothesized that microRNAs (miRNAs) could play a role in the disease process. To determine which miRNAs were changed in expression, miRNA arrays were performed on heart tissue from HCM patients with a MYBPC3 mutation (n=6) and compared with hearts of non-failing donors (n=6). 532 out of 664 analyzed miRNAs were expressed in at least one heart sample. 13 miRNAs were differentially expressed in HCM compared with donors (at p<0.01, fold change ≥ 2). The genomic context of these differentially expressed miRNAs revealed that miR-204 (fold change 2.4 in HCM vs. donor) was located in an intron of the TRPM3 gene, encoding an aspecific cation channel involved in calcium entry. RT-PCR analysis revealed a trend towards TRPM3 upregulation in HCM compared with donor myocardium (fold change 2.3, p=0.078). In silico identification of mRNA targets of differentially expressed miRNAs showed a large proportion of genes involved in cardiac hypertrophy and cardiac beta-adrenergic receptor signaling and we showed reduced phosphorylation of cardiac troponin I in the HCM myocardium when compared with donor. HCM patients with MYBPC3 mutations have a specific miRNA expression profile. Downstream mRNA targets reveal possible involvement in cardiac signaling pathways.
