Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes

被引:1322
作者
Zampetaki, Anna [1 ]
Kiechl, Stefan [3 ]
Drozdov, Ignat [1 ,2 ]
Willeit, Peter [3 ,4 ]
Mayr, Ursula [1 ]
Prokopi, Marianna [1 ]
Mayr, Agnes [5 ,6 ]
Weger, Siegfried [5 ,6 ]
Oberhollenzer, Friedrich [5 ,6 ]
Bonora, Enzo [7 ]
Shah, Ajay [1 ]
Willeit, Johann [3 ]
Mayr, Manuel [1 ]
机构
[1] Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England
[2] Kings Coll London, Ctr Bioinformat, Sch Phys Sci & Engn, London SE5 9NU, England
[3] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria
[4] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
[5] Bruneck Hosp, Dept Lab Med, Brunico, Italy
[6] Bruneck Hosp, Dept Internal Med, Brunico, Italy
[7] Univ Hosp Verona, Div Endocrinol & Metab Dis, Verona, Italy
关键词
diabetes mellitus; microRNA; vascular endothelium; PHOSPHOLIPASE-A2; ACTIVITY; CARDIOVASCULAR-DISEASE; CIRCULATING MICRORNAS; PROTEOMIC ANALYSIS; EXPRESSION; BIOMARKERS; RISK; MICROPARTICLES; NETWORKS; MELLITUS;
D O I
10.1161/CIRCRESAHA.110.226357
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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=2.72x10(-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. (Circ Res. 2010;107:810-817.)
引用
收藏
页码:810 / U359
页数:44
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