Affiliation:
1. From the King's College London British Heart Foundation Centre (A.Z., I.D., U.M., M.P., A.S., M.M.) and Centre for Bioinformatics-School of Physical Sciences and Engineering (I.D.), King's College London, United Kingdom; Department of Neurology (S.K., P.W., J.W.), Medical University Innsbruck, Austria; Department of Public Health and Primary Care (P.W.), University of Cambridge, United Kingdom; Department of Laboratory Medicine and Department of Internal Medicine (A.M., S.W., F.O.), Bruneck Hospital...
Abstract
Rationale:
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.
Methods and 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
1264 articles.
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