title: Circulating microRNAs in obese and lean heart failure patients: A case-control study with computational target prediction analysis.
abstract: OBJECTIVE
  MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and obesity. We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity.
  
  
  METHODS
  In this case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p, and the -221/-130b ratio in 57 age- and gender-matched subjects: 40 HF patients (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was estimated by bioelectrical impedance analysis. MiRs were measured by quantitative reverse transcription-PCR. Bioinformatics analysis was performed based on miRs findings to predict their putative targets and investigate their biological function.
  
  
  RESULTS
  HF was associated with increased miR-423-5p levels in both lean and obese patients (P<0.05 vs. controls) without differences between HF groups. MiR-130b levels were reduced in obese HF patients compared with HF lean (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/-130b ratio was increased in obese HF patients, and was positively associated with body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and waist circumference (r=0.40; P=0.020). Computational prediction of target genes followed by functional enrichment analysis indicated a relevant role of miR-130b and miR-221 in modulating the expression of genes associated to cardiovascular and endocrine diseases, and suggested their influence in important signaling mechanisms and in numerous processes related to the circulatory and endocrine systems.
  
  
  CONCLUSIONS
  In HF patients, the presence of obesity is associated with a differential expression of selected miRs and the miR-221/-130b ratio had significant correlations with adiposity parameters. Computational target prediction analysis identified several interrelated pathways targeted by miR-130b and miR-221 with a known relationship with endocrine and cardiovascular diseases, representing potential mechanisms to be further validated.
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Juliana Gil
authors.initials: JG
authors.lastname: Thomé
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Mariana Recamonde
authors.initials: MR
authors.lastname: Mendoza
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Amanda Veiga
authors.initials: AV
authors.lastname: Cheuiche
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Vanessa Laubert
authors.initials: VL
authors.lastname: La Porta
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Daiane
authors.initials: D
authors.lastname: Silvello
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Kátia Gonçalves
authors.initials: KG
authors.lastname: Dos Santos
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Michael Everton
authors.initials: ME
authors.lastname: Andrades
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Rohde
authors.affiliation: Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental and Molecular Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address: biolo.andreia@gmail.com.
authors.forename: Andréia
authors.initials: A
authors.lastname: Biolo
mesh_terms: D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D013851:Thinness / Q000097:blood* / Q000235:genetics*; D055105:Waist Circumference / Q000235:genetics
chemical_list: D035683:MicroRNAs
keywords: Adiposity; Heart failure; MicroRNA; Obesity; Target prediction