title: The circulating level of FABP3 is an indirect biomarker of microRNA-1.
abstract: OBJECTIVE
  This study sought to identify proteins from the cardiomyocyte (CM) secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1), and thus reflect the pathophysiological state of the CM.
  
  
  BACKGROUND
  MicroRNAs play critical regulatory roles during myocardial remodeling and progression to heart failure. However, it remains unknown whether secreted microRNA-targeted proteins can be used as indicators of myocardial microRNA expression and function.
  
  
  METHODS
  A proteomic analysis based on multidimensional protein identification technology was performed on supernatants from cultured CMs overexpressing miR-1. Biochemical assays and an inducible cardiac-specific transgenic mouse model overexpressing miR-1 were used to demonstrate that heart-type fatty acid-binding protein-3 (FABP3) is a target of miR-1. Levels of miR-1 and FABP3 in cardiac tissue and plasma samples from mouse models as well as human patients were quantified by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The study included wild-type mice subjected to ventricular pressure overload or fasting, as well as patients diagnosed with ventricular hypertrophy due to valvular aortic stenosis, acromegaly, or growth hormone deficiency, conditions associated with altered miR-1 expression.
  
  
  RESULTS
  An inverse relationship between myocardial expression of miR-1 and circulating levels of FABP3 was found both in vitro and in vivo under various pathological conditions.
  
  
  CONCLUSIONS
  Assessment of FABP3 plasma levels in human patients might be used for indirectly measuring cardiac miR-1 activity.
authors.affiliation: IRCCS Multimedica Hospital, Scientific and Technology Pole, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Varrone
authors.forename: Barbara
authors.initials: B
authors.lastname: Gargano
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Carullo
authors.forename: Dario
authors.initials: D
authors.lastname: Di Silvestre
authors.forename: Antonella
authors.initials: A
authors.lastname: De Palma
authors.forename: Ludovica
authors.initials: L
authors.lastname: Grasso
authors.forename: Carolina
authors.initials: C
authors.lastname: Di Somma
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Mauri
authors.forename: Louise
authors.initials: L
authors.lastname: Benazzi
authors.forename: Anna
authors.initials: A
authors.lastname: Franzone
authors.forename: Gloria Saccani
authors.initials: GS
authors.lastname: Jotti
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bang
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
authors.forename: Daniele
authors.initials: D
authors.lastname: Catalucci
mesh_terms: D000172:Acromegaly / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I