PMID- 27150296 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20240117 IS - 1532-429X (Electronic) IS - 1097-6647 (Print) IS - 1097-6647 (Linking) VI - 18 IP - 1 DP - 2016 May 6 TI - Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach. PG - 25 LID - 10.1186/s12968-016-0244-3 [doi] LID - 25 AB - 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*10(5), p = 0.023) but also the circulating miR-222 (OR 938, 95 % CI 938.46, 3.56-24.73*10(4), 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. FAU - Becker, Svetlana AU - Becker S AD - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. FAU - Florian, Anca AU - Florian A AD - Department of Cardiovascular Medicine, University Hospital Munster, Albert-Schweitzer-Campus 1, building A1, 48149, Munster, Germany. FAU - Patrascu, Alexandru AU - Patrascu A AD - Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, Germany. FAU - Rosch, Sabine AU - Rosch S AD - Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, Germany. FAU - Waltenberger, Johannes AU - Waltenberger J AD - Department of Cardiovascular Medicine, University Hospital Munster, Albert-Schweitzer-Campus 1, building A1, 48149, Munster, Germany. FAU - Sechtem, Udo AU - Sechtem U AD - Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, Germany. FAU - Schwab, Matthias AU - Schwab M AD - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. AD - Department of Clinical Pharmacology, University Hospital Tubingen, Tubingen, Germany. AD - Department of Biochemistry and Pharmacy, University Tubingen, Tubingen, Germany. FAU - Schaeffeler, Elke AU - Schaeffeler E AD - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. FAU - Yilmaz, Ali AU - Yilmaz A AD - Department of Cardiovascular Medicine, University Hospital Munster, Albert-Schweitzer-Campus 1, building A1, 48149, Munster, Germany. ali.yilmaz@ukmuenster.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160506 PL - England TA - J Cardiovasc Magn Reson JT - Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance JID - 9815616 RN - 0 (Circulating MicroRNA) RN - 0 (Contrast Media) RN - 0 (Genetic Markers) RN - 0 (MIRN222 microRNA, human) RN - 0 (MIRN26A microRNA, human) RN - 0 (MIRN378 microRNA, human) RN - 0 (MicroRNAs) RN - K2I13DR72L (Gadolinium DTPA) SB - IM MH - Adolescent MH - Adult MH - Area Under Curve MH - Cardiomyopathies/blood/*diagnosis/*diagnostic imaging/genetics MH - Case-Control Studies MH - Circulating MicroRNA/*blood/genetics MH - Contrast Media/administration & dosage MH - Fibrosis MH - Gadolinium DTPA/administration & dosage MH - Gene Expression Profiling/*methods MH - Genetic Markers MH - Heart Ventricles/*diagnostic imaging/pathology/physiopathology MH - Humans MH - *Magnetic Resonance Imaging, Cine MH - Male MH - MicroRNAs/blood/genetics MH - Middle Aged MH - Muscular Dystrophy, Duchenne/*complications/diagnosis MH - Pilot Projects MH - Predictive Value of Tests MH - Prospective Studies MH - ROC Curve MH - Severity of Illness Index MH - Stroke Volume MH - Systole MH - Ventricular Function, Left MH - Ventricular Remodeling MH - Young Adult PMC - PMC4858897 OTO - NOTNLM OT - Cardiomyopathy OT - Cardiovascular magnetic resonance OT - Late gadolinium enhancement OT - Muscular dystrophy OT - miRNA EDAT- 2016/05/07 06:00 MHDA- 2017/12/13 06:00 PMCR- 2016/05/06 CRDT- 2016/05/07 06:00 PHST- 2015/11/19 00:00 [received] PHST- 2016/04/21 00:00 [accepted] PHST- 2016/05/07 06:00 [entrez] PHST- 2016/05/07 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] PHST- 2016/05/06 00:00 [pmc-release] AID - S1097-6647(23)00966-3 [pii] AID - 244 [pii] AID - 10.1186/s12968-016-0244-3 [doi] PST - epublish SO - J Cardiovasc Magn Reson. 2016 May 6;18(1):25. doi: 10.1186/s12968-016-0244-3.