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. 2015 Sep 24:13:314.
doi: 10.1186/s12967-015-0672-0.

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

Lu Fang  1 , Andris H Ellims  2   3 , Xiao-lei Moore  4 , David A White  5 , Andrew J Taylor  6   7 , Jaye Chin-Dusting  8 , Anthony M Dart  9   10   11
Affiliations

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

Lu Fang et al. J Transl Med. .

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 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.

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 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.

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

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Figures

Fig. 1
Fig. 1
Change of plasma miRNAs in patients with lower T1 time identified by miRNA array. Serum/plasma miRNA array was performed on RNA samples isolated from controls, HCM patients with T1 ≥ 470 ms, and with T1 < 470 ms (n = 4/group). Data were expressed as mean ± SEM. *P < 0.05 vs. Ctrl, # P < 0.05 vs. T1 ≥ 470 ms
Fig. 2
Fig. 2
Validation of expression of miRNAs by Taqman real-time PCR. Taqman real-time PCR was performed in 55 HCM patients (n = 28 for T1 ≥ 470 ms and n = 27 for T1 < 470 ms) to validate the findings from miRNA array. In addition, circulating markers of collagen turnover, aminoterminal propeptide of type I collagen (PINP) and aminoterminal propeptide of type III collagen (PIIINP) was measured. Data were expressed as mean ± SEM. *P < 0.05, **P < 0.01
Fig. 3
Fig. 3
Correlations between miRNA levels and postcontrast T1 times. miRNA levels by real-time PCR were significantly and inversely correlated with postcontrast T1 times (except miR-192-5p, miR-296-5p and miR-133a) in 55 HCM patients
Fig. 4
Fig. 4
ROC analysis of the complex of 8 miRNAs (miR-18a-5p, miR-30d-5p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-296-5p, and miR-29a-3p) was used to predict diffuse fibrosis in HCM patients
See this image and copyright information in PMC

References

    1. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation. 2002;105(12):1503–1508. doi: 10.1161/hc1202.105290. - DOI - PubMed
    1. Sabbah HN, Sharov VG, Lesch M, Goldstein S. Progression of heart failure: a role for interstitial fibrosis. Mol Cell Biochem. 1995;147(1–2):29–34. doi: 10.1007/BF00944780. - DOI - PubMed
    1. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476–482. doi: 10.1136/heart.84.5.476. - DOI - PMC - PubMed
    1. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36–44. doi: 10.1016/S0735-1097(99)00492-1. - DOI - PubMed
    1. Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57(8):891–903. doi: 10.1016/j.jacc.2010.11.013. - DOI - PMC - PubMed

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