Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy

Abstract

Background

Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM).

Methods

Cardiac magnetic resonance imaging with postcontrast T ₁ mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T ₁ < 470 ms or T ₁ ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T ₁ time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients.

Results

Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T ₁ < 470 ms compared with those with T ₁ ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T ₁ values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663–0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis.

Conclusions

These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.

Electronic supplementary material

The online version of this article (doi:10.1186/s12967-015-0672-0) contains supplementary material, which is available to authorized users.