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

Journal of Cardiovascular Magnetic Resonance

Research

Anca Florian¹  Ali Yilmaz¹  Johannes Waltenberger¹  Sabine Rösch²  Alexandru Patrascu²  Udo Sechtem²  Svetlana Becker³  Elke Schaeffeler³  Matthias Schwab⁴ 

[1] Department of Cardiovascular Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, 48149, Münster, Germany;Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, Germany;Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany;Department of Biochemistry and Pharmacy, University Tübingen, Tübingen, Germany;

关键词: miRNA;    Cardiomyopathy;    Muscular dystrophy;    Cardiovascular magnetic resonance;    Late gadolinium enhancement;   

DOI  :  10.1186/s12968-016-0244-3

 received in 2015-11-19, accepted in 2016-04-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDuchenne 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.MethodsSixty-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.ResultsAn 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).ConclusionsUp-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.

【 授权许可】

CC BY   
© Becker et al. 2016