Abstract
BackgroundCirculating 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).MethodsCardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T1 < 470 ms or T1 ≥ 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 T1 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.ResultsAmong 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 T1 < 470 ms compared with those with T1 ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T1 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.ConclusionsThese findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0672-0) contains supplementary material, which is available to authorized users.
Highlights
Circulating microRNAs may represent novel markers for cardiovascular diseases
We aimed to study: (1) changes of plasma miRNAs in hypertrophic cardio‐ myopathy (HCM) patients with diffuse myocardial fibrosis indicated by lower T1 times, as compared with patients without diffuse fibrosis or healthy controls, (2) the correlations between circulating miRNA levels and postcontrast myocardial T1 times, and diagnostic values of circulating miRNA levels for the detection of diffuse fibrosis
Postcontrast myocardial T1 times excluding late gadolinium enhancement (LGE) and including LGE were shown in Tables 1 and 2
Summary
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 cardio‐ myopathy (HCM). Myocardial fibrosis, a hallmark of various cardiovascular diseases, contributes to heart failure, arrhythmias and sudden death [1, 2]. Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease and myocardial fibrosis is a common and early feature of HCM [3], associated with the poor prognosis in HCM patients [3, 4]. Myocardial fibrosis could only be definitively diagnosed with cardiac biopsies. There are currently no reliable serological biomarkers to detect myocardial fibrosis. Recent studies have introduced cardiac magnetic resonance imaging (CMR) to noninvasively diagnose myocardial fibrosis [5].
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