title: Circulating microRNA-150-5p as a novel biomarker for advanced heart failure: A genome-wide prospective study.
abstract: BACKGROUND
  Circulating microRNAs (miRs) are promising biomarkers for heart failure (HF). Previous studies have provided inconsistent miR "signatures." The phenotypic and pathophysiologic heterogeneity of HF may have contributed to this inconsistency. In this study we assessed whether advanced HF (AHF) patients present a distinct miR signature compared with healthy subjects (HS) and mild to moderate HF (MHF) patients.
  
  
  METHODS
  The study consisted of 2 phases: a screening phase and a validation phase. In the screening phase, 752 miRs were profiled in HS and MHF and AHF patients (N = 15), using the real-time quantitative polymerase chain reaction (RT-qPCR) technique and global mean normalization. In the validation phase, the miRs found to be significantly dysregulated in AHF patients compared with both HS and MHF patients were validated in 15 HS, 25 patients with MHF and 29 with AHF, using RT-qPCR, and normalizing to exogenous (cel-miR-39) and endogenous controls.
  
  
  RESULTS
  In the screening phase, 5 miRs were found to be significantly dysregulated: -26a-5p; -145-3p; -150-5p; -485-3p; and -487b-3p. In the validation phase, miR-150-5p was confirmed to be significantly downregulated in AHF patients when compared with both HS and MHF patients, irrespective of the normalization method used. miR-26a-5p was confirmed to be significantly dysregulated only when normalized to cell-miR-39. Dysregulation of the other miRs could not be confirmed. miR-150-5p was significantly associated with maladaptive remodeling, disease severity and outcome.
  
  
  CONCLUSIONS
  Our data suggest miR-150-5p as a novel circulating biomarker for AHF. The association of miR-150-5p with maladaptive remodeling, disease severity and outcome supports the pathophysiologic relevance of downregulated miR-150-5p expression to AHF.
authors.affiliation: Department of Cardiology and Cardiac Rehabilitation. Scientific Clinical Institutes Maugeri, IRCCS Institute of Cassano Murge, Bari, Italy. Electronic address: domenico.scrutinio@icsmaugeri.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Scrutinio
authors.affiliation: Department of Cardiology and Cardiac Rehabilitation. Scientific Clinical Institutes Maugeri, IRCCS Institute of Cassano Murge, Bari, Italy; Division of Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conserva
authors.affiliation: Department of Cardiology and Cardiac Rehabilitation. Scientific Clinical Institutes Maugeri, IRCCS Institute of Cassano Murge, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Passantino
authors.affiliation: Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Iacoviello
authors.affiliation: Department of Cardiology and Cardiac Rehabilitation. Scientific Clinical Institutes Maugeri, IRCCS Institute of Cassano Murge, Bari, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Lagioia
authors.affiliation: Division of Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012313:RNA; C533097:MIR150, human
keywords: advanced heart failure; adverse remodeling; biomarker; microRNA; outcome