title: miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study.
abstract: OBJECTIVE
  MicroRNAs are small non-coding RNAs that inversely regulate their target gene expression. The whole miRNA profile of human atherosclerotic plaques has not been studied previously. The aim of this study was to investigate the miRNA expression profile in human atherosclerotic plaques as compared to non-atherosclerotic left internal thoracic arteries (LITA), and to connect this expression to the processes in atherosclerosis.
  
  
  METHODS
  The miRNA expression profiles of six LITAs and 12 atherosclerotic plaques obtained from aortic, carotid, and femoral atherosclerotic arteries from Tampere Vascular Study were analyzed. The analyses were performed with Agilent's miRNA Microarray. The expression levels of over 4-fold up-regulated miRNAs were verified with qRT-PCR from a larger population (n=50). Messenger RNA levels were analyzed with Illumina's Expression BeadChip to study miRNA target expression.
  
  
  RESULTS
  Ten miRNAs were found to be differently expressed in atherosclerotic plaques when compared to controls (p<0.05). The expression of miR-21, -34a, -146a, -146b-5p, and -210 was verified and found to be significantly up-regulated in atherosclerotic arteries versus LITAs (p<0.001, fold changes 4.61, 2.55, 2.87, 2.82, and 3.92, respectively). Several predicted targets of these miRNAs were down-regulated, and gene set enrichment analysis showed several pathways which could be differently expressed due to this miRNA profile.
  
  
  CONCLUSIONS
  The microRNA expression profile differs significantly between atherosclerotic plaques and control arteries. The most up-regulated miRNAs are involved in processes known to be connected to atherosclerosis. Interfering with the miRNA expression in the artery wall is a potential way to affect atherosclerotic plaque and cardiovascular disease development.
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital and the Medical School at the University of Tampere, Tampere, Finland. emma.raitoharju@uta.fi
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Mari
authors.initials: M
authors.lastname: Levula
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.forename: Ari
authors.initials: A
authors.lastname: Mennander
authors.forename: Matti
authors.initials: M
authors.lastname: Tarkka
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000368:Aged; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000737:chemistry; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C542542:MIRN146 microRNA, human; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs