title: Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is caused by mutations in different structural genes and induces pathological hypertrophy with sudden cardiac death as a possible consequence. HCM can be separated into hypertrophic non-obstructive and obstructive cardiomyopathy (HNCM/HOCM) with different clinical treatment approaches. We here distinguished between HNCM, HOCM, cardiac amyloidosis and aortic stenosis by using microRNA profiling and investigated potential interactions between circulating miRNA levels and the most common mutations in MYH7and MYBPC3 genes.
  
  
  METHODS
  Our study included 4 different groups: 23 patients with HNCM, 28 patients with HOCM, 47 patients with aortic stenosis and 22 healthy controls. Based on previous findings, 8 different cardiovascular known microRNAs (miR-1, miR-21, miR-29a, miR-29b, miR-29c, miR-133a, miR-155 and miR-499) were studied in serum of all patients and compared with clinically available patient data.
  
  
  RESULTS
  We found miR-29a levels to be increased in patients with HOCM and correlating markers of cardiac hypertrophy. This was not the case in HNCM patients. In contrast, we identified miR-29c to be upregulated in aortic stenosis but not the other patient groups. ROC curve analysis of miR-29a/c distinguished between HOCM patients and aortic stenosis patients. MiR-29a and miR-155 levels discriminated HNCM patients from patients with senile cardiac amyloidosis. MiR-29a increased mainly in HOCM patients with a mutation in MYH7, whereas miR-155 was decreased in hypertrophic cardiomyopathy patients with a mutation in MYBPC3.
  
  
  CONCLUSIONS
  We demonstrated that miR-29a and miR-29c show a specific signature to distinguish between aortic stenosis, hypertrophic non-obstructive and obstructive cardiomyopathies and thus could be developed into clinically useful biomarkers.
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: Anselm A
authors.initials: AA
authors.lastname: Derda
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Thum
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: Johan M
authors.initials: JM
authors.lastname: Lorenzen
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bavendiek
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heineke
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Keyser
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York, NY, 10032.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Givens
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York, NY, 10032.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kennel
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York, NY, 10032.
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Julian D
authors.initials: JD
authors.lastname: Widder
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; National Heart and Lung Institute, Imperial College London, UK. Electronic address: thum.thomas@mh-hannover.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000235:genetics; D001024:Aortic Valve Stenosis / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000145:classification / Q000175:diagnosis*; D002352:Carrier Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics; D016133:Polymerase Chain Reaction; D000099163:Myosin Binding Protein C
chemical_list: D015415:Biomarkers; D024722:Cardiac Myosins; D002352:Carrier Proteins; D035683:MicroRNAs; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C532045:MIRN29a microRNA, human; C501641:MYH7 protein, human
keywords: Amyloidosis; Aortic stenosis; Biomarker; Diagnosis; Hypertrophic cardiomyopathies; MicroRNA