PMID- 30622476
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 9
DP  - 2018
TI  - Identification of Cardiomyopathy-Associated Circulating miRNA Biomarkers in 
      Muscular Dystrophy Female Carriers Using a Complementary Cardiac Imaging and 
      Plasma Profiling Approach.
PG  - 1770
LID - 10.3389/fphys.2018.01770 [doi]
LID - 1770
AB  - Background: Different from males with Duchenne/Becker muscular dystrophy 
      (DMD/BMD) in whom overt myopathy is the rule, muscular dystrophy (MD) female 
      carriers are mostly free of skeletal muscle symptoms. However, similar to MD 
      males, these females are also prone to cardiomyopathy. Since circulating 
      microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various 
      cardiovascular diseases, the aim of the current study was to identify specific 
      circulating miRNAs in the plasma of female DMD/BMD carriers that may allow an 
      early and accurate diagnosis of cardiac involvement in these cases. Methods: 
      Twenty-nine female MD carriers and 24 age-matched healthy female controls were 
      prospectively enrolled. All MD carriers 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 was 
      detected in 4 (14%) MD carriers while late gadolinium enhancement (LGE) 
      indicative of myocardial fibrosis was present in 13 female patients (45%)-with an 
      exclusively non-ischemic pattern. Among the circulating miRNAs examined, six were 
      significantly up-regulated in MD carriers compared to female controls: miR-206 
      (103-fold increase, p < 0.0001), miR-222 (41-fold, p < 0.0001), miR-26a 
      (fourfold, p = 0.029), miR-342 (27-fold, p < 0.0001), miR-378a-3p (minimum 
      3,600-fold; almost undetectable in controls, p = 0.013), miR-378a-5p (64-fold, p 
      < 0.0001); only two miRNAs were substantially down-regulated in MD carriers: 
      miR-144 (p < 0.0001) and miR-29a (p = 0.002) (both undetectable in carriers). A 
      significant down-regulation of the miR-29c (<0.001-fold, p = 0.006) was observed 
      in MD carriers with abnormal CMR findings (comprising functional and/or 
      structural abnormalities) compared to those with normal CMR examinations. 
      Univariable analyses regarding the presence of abnormal CMR findings resulted in 
      four significant variables: LV end-diastolic volume index (EDVi), LV end-systolic 
      volume index (ESVi), an elevated plasma creatine kinase (CK), and decreased serum 
      miR-29c levels. In subsequent multivariable analysis, the only independent 
      predictor for an abnormal CMR among MD carriers was circulating miR-29c (OR 0.99, 
      95% CI 0.98-0.99, p = 0.037). Moreover, an elevated CK and/or a downregulated 
      miR-29c level (<0.05 x 10(-3)) resulted in an improved AUC value of 0.79 
      (0.62-0.97, p = 0.007) (79, 80 and 80%, sensitivity, specificity and overall 
      accuracy) for the CMR-based diagnosis of cardiomyopathy in MD carriers when 
      compared to using the two parameters individually. Conclusion: In female MD 
      carriers, down-regulation of circulating miR-29c relates to the presence of 
      functional and/or structural cardiac abnormalities (as detected by CMR) and 
      appears to be a promising novel biomarker-in addition to conventional CK plasma 
      levels-for an early diagnosis of cardiomyopathy.
FAU - Florian, Anca
AU  - Florian A
AD  - Department of Cardiology, University Hospital Munster, Munster, Germany.
FAU - Patrascu, Alexandru
AU  - Patrascu A
AD  - Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, Germany.
FAU - Tremmel, Roman
AU  - Tremmel R
AD  - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, 
      Germany.
FAU - Rosch, Sabine
AU  - Rosch S
AD  - Division of Cardiology, Robert-Bosch-Hospital, Stuttgart, 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, Institute of Experimental and Clinical 
      Pharmacology and Toxicology, University Hospital Tubingen, Tubingen, Germany.
AD  - Department of Pharmacy and Biochemistry, University of 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 Cardiology, University Hospital Munster, Munster, Germany.
LA  - eng
PT  - Journal Article
DEP - 20181221
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6308188
OTO - NOTNLM
OT  - cardiomyopathy
OT  - cardiovascular magnetic resonance
OT  - female carriers
OT  - microRNA
OT  - muscular dystrophy
EDAT- 2019/01/10 06:00
MHDA- 2019/01/10 06:01
PMCR- 2018/12/21
CRDT- 2019/01/10 06:00
PHST- 2018/08/14 00:00 [received]
PHST- 2018/11/23 00:00 [accepted]
PHST- 2019/01/10 06:00 [entrez]
PHST- 2019/01/10 06:00 [pubmed]
PHST- 2019/01/10 06:01 [medline]
PHST- 2018/12/21 00:00 [pmc-release]
AID - 10.3389/fphys.2018.01770 [doi]
PST - epublish
SO  - Front Physiol. 2018 Dec 21;9:1770. doi: 10.3389/fphys.2018.01770. eCollection 
      2018.