Circulating microRNAs in obese and lean heart failure patients: A case–control study with computational target prediction analysis

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. In this case–control study, we compared plasma levels of miR-21, -130b, -221, -423-5p,...

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Veröffentlicht in:Gene 2015-12, Vol.574 (1), p.1-10
Hauptverfasser: Thomé, Juliana Gil, Mendoza, Mariana Recamonde, Cheuiche, Amanda Veiga, La Porta, Vanessa Laubert, Silvello, Daiane, dos Santos, Kátia Gonçalves, Andrades, Michael Everton, Clausell, Nadine, Rohde, Luis Eduardo, Biolo, Andréia
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container_title Gene
container_volume 574
creator Thomé, Juliana Gil
Mendoza, Mariana Recamonde
Cheuiche, Amanda Veiga
La Porta, Vanessa Laubert
Silvello, Daiane
dos Santos, Kátia Gonçalves
Andrades, Michael Everton
Clausell, Nadine
Rohde, Luis Eduardo
Biolo, Andréia
description 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. 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. HF was associated with increased miR-423-5p levels in both lean and obese patients (P
doi_str_mv 10.1016/j.gene.2015.07.068
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We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. 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. HF was associated with increased miR-423-5p levels in both lean and obese patients (P&lt;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. 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. •In HF patients, obesity is associated with altered expression of miR-130b and miR-221.•The ratio miR-221/-130b has positive correlation with adiposity parameters.•Predicted miR targets are highly enriched in cardiovascular and endocrine diseases.•Bioinformatics analysis reveals that these miRs modulate important signaling pathways.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2015.07.068</identifier><identifier>PMID: 26211628</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adiposity ; Body Composition - genetics ; Body Mass Index ; Case-Control Studies ; Computational Biology - methods ; Female ; Heart failure ; Heart Failure - blood ; Heart Failure - genetics ; Humans ; Male ; MicroRNA ; MicroRNAs - blood ; MicroRNAs - genetics ; Middle Aged ; Obesity ; Obesity - blood ; Obesity - genetics ; Target prediction ; Thinness - blood ; Thinness - genetics ; Waist Circumference - genetics</subject><ispartof>Gene, 2015-12, Vol.574 (1), p.1-10</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. 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We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. 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. HF was associated with increased miR-423-5p levels in both lean and obese patients (P&lt;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. 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We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. 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. HF was associated with increased miR-423-5p levels in both lean and obese patients (P&lt;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. 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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. •In HF patients, obesity is associated with altered expression of miR-130b and miR-221.•The ratio miR-221/-130b has positive correlation with adiposity parameters.•Predicted miR targets are highly enriched in cardiovascular and endocrine diseases.•Bioinformatics analysis reveals that these miRs modulate important signaling pathways.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26211628</pmid><doi>10.1016/j.gene.2015.07.068</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5231-2071</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adiposity
Body Composition - genetics
Body Mass Index
Case-Control Studies
Computational Biology - methods
Female
Heart failure
Heart Failure - blood
Heart Failure - genetics
Humans
Male
MicroRNA
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
Obesity
Obesity - blood
Obesity - genetics
Target prediction
Thinness - blood
Thinness - genetics
Waist Circumference - genetics
title Circulating microRNAs in obese and lean heart failure patients: A case–control study with computational target prediction analysis
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