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Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
Published on: September 15, 2018
Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy
Anselm A Derda1, Sabrina Thum1, Johan M Lorenzen1
1Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany.
Insights
MicroRNAs miR-29a and miR-29c can distinguish between hypertrophic obstructive cardiomyopathy (HOCM) and other heart conditions like aortic stenosis. These specific microRNA signatures may serve as valuable diagnostic biomarkers for cardiac diseases.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- Hypertrophic cardiomyopathy (HCM) arises from genetic mutations, leading to pathological cardiac hypertrophy and potential sudden cardiac death.
- HCM is classified into hypertrophic non-obstructive (HNCM) and obstructive (HOCM) types, requiring distinct clinical management strategies.
- Differentiating HCM subtypes, cardiac amyloidosis, and aortic stenosis is crucial for effective treatment.
Purpose of the Study:
- To investigate microRNA (miRNA) profiles in patients with HNCM, HOCM, aortic stenosis, and healthy controls.
- To explore potential correlations between circulating miRNA levels and common mutations in MYH7 and MYBPC3 genes in HCM.
- To identify specific miRNAs that can serve as biomarkers for distinguishing between these cardiovascular conditions.
Main Methods:
- Serum samples were collected from 23 HNCM patients, 28 HOCM patients, 47 aortic stenosis patients, and 22 healthy controls.
- Quantitative analysis of eight cardiovascular-related miRNAs (miR-1, miR-21, miR-29a, miR-29b, miR-29c, miR-133a, miR-155, miR-499) was performed.
- Patient data, including clinical information and genetic mutations, were compared with miRNA expression levels.
Main Results:
- miR-29a levels were elevated in HOCM patients, correlating with cardiac hypertrophy markers, but not in HNCM patients.
- miR-29c was upregulated in aortic stenosis patients, showing a distinct expression pattern.
- Receiver operating characteristic (ROC) curve analysis using miR-29a/c effectively distinguished between HOCM and aortic stenosis.
- miR-29a and miR-155 levels differentiated HNCM from cardiac amyloidosis.
- Specific correlations were observed between miR-29a and MYH7 mutations, and miR-155 and MYBPC3 mutations in HCM.
Conclusions:
- miR-29a and miR-29c exhibit specific expression patterns that can differentiate between aortic stenosis, HNCM, and HOCM.
- These miRNAs hold potential for development into clinically applicable biomarkers for diagnosing and differentiating cardiovascular diseases.
- The study highlights the utility of miRNA profiling in understanding the molecular basis of distinct cardiac pathologies.
Background:
Hypertrophic cardiomyopathy (HCM) is caused by mutations in different structural genes and induces pathological hypertrophy with sudden cardiac death as a possible consequence. HCM can be separated into hypertrophic non-obstructive and obstructive cardiomyopathy (HNCM/HOCM) with different clinical treatment approaches. We here distinguished between HNCM, HOCM, cardiac amyloidosis and aortic stenosis by using microRNA profiling and investigated potential interactions between circulating miRNA levels and the most common mutations in MYH7and MYBPC3 genes.
Methods:
Our study included 4 different groups: 23 patients with HNCM, 28 patients with HOCM, 47 patients with aortic stenosis and 22 healthy controls. Based on previous findings, 8 different cardiovascular known microRNAs (miR-1, miR-21, miR-29a, miR-29b, miR-29c, miR-133a, miR-155 and miR-499) were studied in serum of all patients and compared with clinically available patient data.
Results:
We found miR-29a levels to be increased in patients with HOCM and correlating markers of cardiac hypertrophy. This was not the case in HNCM patients. In contrast, we identified miR-29c to be upregulated in aortic stenosis but not the other patient groups. ROC curve analysis of miR-29a/c distinguished between HOCM patients and aortic stenosis patients. MiR-29a and miR-155 levels discriminated HNCM patients from patients with senile cardiac amyloidosis. MiR-29a increased mainly in HOCM patients with a mutation in MYH7, whereas miR-155 was decreased in hypertrophic cardiomyopathy patients with a mutation in MYBPC3.
Conclusion:
We demonstrated that miR-29a and miR-29c show a specific signature to distinguish between aortic stenosis, hypertrophic non-obstructive and obstructive cardiomyopathies and thus could be developed into clinically useful biomarkers.
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