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Journal of Cardiovascular Magnetic Resonance
Published in: Journal of Cardiovascular Magnetic Resonance 1/2017

Open Access 01-12-2016 | Research

Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach

Authors: Svetlana Becker, Anca Florian, Alexandru Patrascu, Sabine Rösch, Johannes Waltenberger, Udo Sechtem, Matthias Schwab, Elke Schaeffeler, Ali Yilmaz

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2017

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Abstract

Background

Duchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far.

Methods

Sixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day.

Results

An impaired left ventricular (LV) systolic function (defined as LV-EF <55 %) was detected in 29 (46 %) and presence of late gadolinium enhancement (LGE) indicative of myocardial fibrosis in 48 (76 %) MD patients with an exclusively non-ischemic pattern. Whereas no significant differences were observed for the 27 selected circulating miRNAs in MD patients with abnormal CMR findings (comprising structural and/or functional impairments) compared to those with completely normal CMR studies, a significant up-regulation of three miRNAs was observed in LGE-positive MD patients compared to LGE-negative ones: miR-222 (1.8-fold, p = 0.035), miR-26a (2.1-fold, p = 0.03) and miR-378a-5p (2.4-fold, p = 0.026). A signature of these three miRNAs (miR-26a, miR-222 and miR-378a-5p) resulted in an area under the curve (AUC) value of 0.74 for the diagnosis of LGE-positive MD patients. In a multivariable model, three independent predictors for LGE presence were identified comprising not only clinical and laboratory markers (LV-EF: OR 0.47, 95 % CI 0.24-0.89, p = 0.021 and elevated hs-Trop: OR 2559, 95 % CI 2.97-22.04*105, p = 0.023) but also the circulating miR-222 (OR 938, 95 % CI 938.46, 3.56-24.73*104, p = 0.016).

Conclusions

Up-regulation of circulating miRNAs miR-222, miR-26a and miR-378a-5p indicates the presence of myocardial scars in MD patients. Plasma miR-222 appears to be a promising novel biomarker reflecting structural – but not functional – cardiac alterations in MD patients.
Appendix
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Metadata
Title
Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach
Authors
Svetlana Becker
Anca Florian
Alexandru Patrascu
Sabine Rösch
Johannes Waltenberger
Udo Sechtem
Matthias Schwab
Elke Schaeffeler
Ali Yilmaz
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2017
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/s12968-016-0244-3

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