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Published on: January 7, 2018
Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance
Alessandra Giannella1, Claudia Maria Radu1, Lorenzo Franco2
1Department of Medicine-DIMED, University of Padova, Padua, Italy.
Background:
Microparticles (MPs) are vesicular structures shed from endothelial or circulating blood cells, after activation or apoptosis, and can be considered markers of vascular damage. We aimed to determine the levels of circulating MPs, their content of miRNA-126-3p and 5p, and their relationship with early endothelial activation/damage, in patients with different degree of glucose tolerance.
Methods:
CD62E+, CD62P+, CD142+, CD45+ circulating MPs, their apoptotic (AnnexinV+) fractions, and miRNA-126 expression were determined in 39 prediabetic (PreDM), 68 type 2 diabetic (T2DM), and 53 control (NGT) subjects, along with main anthropometric and biochemical measurements. MPs were analysed by flow cytometry. miRNA-126 was measured by quantitative real-time PCR. Plasma antioxidant capacity was determined by electronic spin resonance; ICAM-1, and VCAM-1 by ELISA.
Results:
Activated endothelial cell-derived MPs (CD62E+) were significantly increased in PreDM and T2DM in comparison to NGT (p < 0.0001). AnnexinV+/CD62E+ MPs and Annexin V+ MPs were significantly increased in T2DM compared to PreDM and NGT (p < 0.001); other MPs were not significantly different among groups. Plasma antioxidant capacity was significantly decreased in PreDM and T2DM compared to NGT (p = 0.001); VCAM-1 significantly increased in PreDM and T2DM in comparison to NGT (p = 0.001). miR-126-3p expression, but not miR-126-5p, in MPs, decreased significantly and progressively from NGT, to PreDM, and T2DM (p < 0.001). In PreDM and T2DM, CD62E+ MPs level was significantly and negatively associated with plasma glucose (p = 0.004).
Conclusion:
We show for the first time that circulating CD62E+ MPs level and miR-126-3p content in MPs are abnormal in subjects with pre-diabetes; the content of miR-126-3p correlates with markers of endothelial inflammation, such as VCAM-1, plasma antioxidant capacity, and microparticles, well-accepted markers of endothelial dysfunction.
Insights
Circulating microparticles (MPs) and miR-126-3p levels are altered in prediabetes and type 2 diabetes, indicating early endothelial dysfunction. These findings highlight potential biomarkers for vascular damage in glucose intolerance.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Molecular Biology
Background:
- Microparticles (MPs) are shed from blood cells and indicate vascular damage.
- Early endothelial activation and damage are key in glucose intolerance.
Purpose of the Study:
- To determine circulating MP levels and miRNA-126 content in prediabetes and type 2 diabetes.
- To investigate the relationship between MPs, miRNA-126, and early endothelial dysfunction markers.
Main Methods:
- Flow cytometry was used to analyze MPs (CD62E+, CD62P+, CD142+, CD45+) and apoptotic fractions (AnnexinV+) in 39 prediabetic (PreDM), 68 type 2 diabetic (T2DM), and 53 normal glucose tolerance (NGT) subjects.
- Quantitative real-time PCR measured miRNA-126 expression in MPs.
- Plasma antioxidant capacity, ICAM-1, and VCAM-1 were assessed.
Main Results:
- Activated endothelial cell-derived MPs (CD62E+) were significantly increased in PreDM and T2DM compared to NGT.
- miR-126-3p expression in MPs decreased progressively from NGT to PreDM to T2DM.
- Decreased plasma antioxidant capacity and increased VCAM-1 were observed in PreDM and T2DM.
Conclusions:
- Circulating CD62E+ MPs and miR-126-3p content are abnormal in prediabetes, suggesting early endothelial dysfunction.
- miR-126-3p levels correlate with markers of endothelial inflammation and dysfunction, including VCAM-1 and antioxidant capacity.
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