title: Decreased miR-181a expression in monocytes of obese patients is associated with the occurrence of metabolic syndrome and coronary artery disease.
abstract: BACKGROUND
  Inflammation during obesity is associated with higher risk of metabolic syndrome and coronary artery disease (CAD). Activation of the inflammatory toll-like receptor (TLR)/nuclear factor κB (NFκB) signaling in monocytes contributes to inflammation. Weight loss after bariatric surgery leads to significant improvement of obesity-related comorbidities. MicroRNA (miR), a class of small noncoding RNA, have been implicated as negative regulators of inflammatory processes.
  
  
  OBJECTIVE
  This study sought to identify dysregulated miR in monocytes of obese patients associated with TLR/NFκB signaling, metabolic syndrome, and CAD.
  
  
  METHODS
  This retrospective study included two independent cohorts of 21 morbidly obese and 125 high-risk obese and nonobese patients in a hospitalized care setting.
  
  
  METHODS
  INTERVENTION included bariatric surgery (n = 21) with a 3-month follow-up.
  
  
  METHODS
  miR expressions in CD14(+) monocytes were determined by microarray analysis. TLR/NFκB-related miR were identified by an in silico target prediction analysis. Their expression was validated by quantitative RT-PCR. Their association with metabolic syndrome and angiographically documented CAD was assessed.
  
  
  RESULTS
  miR-181a, -181b, and -181d, identified as possible regulators of the TLR/NFκB signaling, were decreased in obese monocytes, and weight loss normalized their expression to levels observed in monocytes of lean persons. miR-181a but not miR-181b and miR-181d was associated with a higher number of metabolic syndrome components and with CAD even after adjustment for traditional risk factors, obesity and the metabolic syndrome.
  
  
  CONCLUSIONS
  This study demonstrates that the TLR/NFκB-related miR-181a is down-regulated in monocytes of obese patients and suggests that it is a putative biomarker of metabolic syndrome and CAD.
authors.affiliation: Atherosclerosis and Metabolism Unit, Katholieke Universiteit Leuven, Herestraat 49, PB 705, 3000 Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Hulsmans
authors.forename: Peter
authors.initials: P
authors.lastname: Sinnaeve
authors.forename: Bart
authors.initials: B
authors.lastname: Van der Schueren
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
mesh_terms: D000328:Adult; D050110:Bariatric Surgery / Q000534:rehabilitation; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D015994:Incidence; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D054928:Validation Studies as Topic
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs