title: Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.
abstract: OBJECTIVE
  The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis.
  
  
  BACKGROUND
  miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised.
  
  
  METHODS
  Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors.
  
  
  RESULTS
  Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis.
  
  
  CONCLUSIONS
  Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM.
authors.affiliation: Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy; Multimedica Research Hospital, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Roncarati
authors.affiliation: Multimedica Research Hospital, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Viviani Anselmi
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Losi
authors.affiliation: Multimedica Research Hospital, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Papa
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnology, La Sapienza University of Rome, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cavarretta
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
authors.forename: Paula
authors.initials: P
authors.lastname: Da Costa Martins
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Contaldi
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Saccani Jotti
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Franzone
authors.affiliation: AVIS Comunale Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Galastri
authors.affiliation: Humanitas Clinical and Research Center and University of Milan, Rozzano, Italy.
authors.forename: Michael V G
authors.initials: MV
authors.lastname: Latronico
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Imbriaco
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
authors.forename: Leon
authors.initials: L
authors.lastname: De Windt
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Electronic address: sandro.betocchi@unina.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Betocchi
authors.affiliation: Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy; Humanitas Clinical and Research Center and University of Milan, Rozzano, Italy. Electronic address: gianluigi.condorelli@unimi.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000235:genetics; D006801:Humans; D006984:Hypertrophy / Q000097:blood / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C532045:MIRN29a microRNA, human; D035683:MicroRNAs
keywords: circulating microRNAs; fibrosis; hypertrophic cardiomyopathy; myocardial remodeling