Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes.
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.
Zampetaki
Anna
A
King's British Heart Foundation Centre, King's College London, United Kingdom.
Kiechl
Stefan
S
Drozdov
Ignat
I
Willeit
Peter
P
Mayr
Ursula
U
Prokopi
Marianna
M
Mayr
Agnes
A
Weger
Siegfried
S
Oberhollenzer
Friedrich
F
Bonora
Enzo
E
Shah
Ajay
A
Willeit
Johann
J
Mayr
Manuel
M
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
D005819:Genetic Markers; C527111:MIRN126 microRNA, human; D035683:MicroRNAs