Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy

Abstract

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.

The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

“…The increase in Hcn2 mRNA atrial expression at baseline was expected (Fig. 2D) because we have previously observed that TRβ Δ337T mice exhibit significant increases in heart rate [52] under baseline conditions compared with TRβ WT animals with a cardiac phenotype very similar to hyperthyroidism. This increased HR occurs because the TRβ Δ337T animals have high serum concentrations of TH, which interact with THRα1.…”

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients

“…PLSR analysis gave quantitative outputs to how likely each microRNA was involved in our response. Certain microRNA’s identified by our anaylsis have been shown to regulate important function like fibrosis (miR-27a and miR-29c 26, 27 ), cardiac hypertrophy (miR-29c 28 , miR-96 29, 30 , miR-182 31, 32 and miR-185 33 ), angiogenesis (miR-27a 34 ), and apoptotsis (miR-138 35, 36 , miR-25 37 ). Although, our model is predictive of microRNA-based mechanism, these targets still need to be validated in the future studies.…”

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

“…Several miRNAs have recently been linked to the diagnosis of HF 34, 35. Based on our screening results as well as literature findings,36, 37 several ‘cardiac remodelling’‐associated miRNAs and lncRNAs have been chosen to be tested in the FIBROTARGETS patient populations to determine their use for improving diagnosis of HF, risk and patient stratification, and prediction of individual patient prognosis. Standardized miRNA‐ or lncRNA‐specific PCR‐based protocols and normalization procedures are currently being used to achieve this goal.…”