title: Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have been implicated in the epigenetic regulation of key metabolic, inflammatory, and antiangiogenic pathways in type 2 diabetes (DM) and may contribute to common disease complications.
  
  
  OBJECTIVE
  In this study, we explore plasma miRNA profiles in patients with DM.
  
  
  RESULTS
  Total RNA was extracted from plasma samples of the prospective population-based Bruneck study. A total of 13 candidate miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls (1995 evaluation, n=80 each). Quantitative PCR assessment revealed lower plasma levels of miR-20b, miR-21, miR-24, miR-15a, miR-126, miR-191, miR-197, miR-223, miR-320, and miR-486 in prevalent DM, but a modest increase of miR-28-3p. Findings emerged as robust in multivariable analysis and were independent of the standardization procedure applied. For endothelial miR-126, results were confirmed in the entire Bruneck cohort (n=822) in univariate (odds ratio [95% confidence interval], 0.38 [0.26 to 0.55]; P=2.72 × 10(-7)) and multivariate analyses (0.57 [0.37 to 0.86]; P=0.0082). Importantly, reduced miR-15a, miR-29b, miR-126, miR-223, and elevated miR-28-3p levels antedated the manifestation of disease. Most differences in miRNA levels were replicated in plasma obtained from hyperglycemic Lep(ob) mice. High glucose concentrations reduced the miR-126 content of endothelial apoptotic bodies. Similarly in patients with DM, the reduction of miR-126 was confined to circulating vesicles in plasma.
  
  
  CONCLUSIONS
  We reveal a plasma miRNA signature for DM that includes loss of endothelial miR-126. These findings might explain the impaired peripheral angiogenic signaling in patients with DM.
authors.affiliation: King's British Heart Foundation Centre, King's College London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Zampetaki
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Ignat
authors.initials: I
authors.lastname: Drozdov
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.forename: Ursula
authors.initials: U
authors.lastname: Mayr
authors.forename: Marianna
authors.initials: M
authors.lastname: Prokopi
authors.forename: Agnes
authors.initials: A
authors.lastname: Mayr
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Oberhollenzer
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Ajay
authors.initials: A
authors.lastname: Shah
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D005819:Genetic Markers; C527111:MIRN126 microRNA, human; D035683:MicroRNAs