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Int. J. Mol. Sci. 2018, 19(10), 3242; https://doi.org/10.3390/ijms19103242

Anti-Angiogenic miR-222, miR-195, and miR-21a Plasma Levels in T1DM Are Improved by Metformin Therapy, Thus Elucidating Its Cardioprotective Effect: The MERIT Study

1
Department of Diabetes, Queen Elizabeth Hospital, Gateshead, Newcastle Upon Tyne NE9 6SH, UK
2
Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
3
Department of Diabetes and Endocrinology, Royal Sussex County Hospital, Brighton BN2 5BE, UK
4
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah P.O. Box 80218, Saudi Arabia
5
Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah P.O. Box 80216, Saudi Arabia
6
Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
7
Cardiovascular Research Centre, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
*
Author to whom correspondence should be addressed.
Received: 27 July 2018 / Revised: 4 September 2018 / Accepted: 6 September 2018 / Published: 19 October 2018
(This article belongs to the Special Issue Metformin: Mechanism and Application)
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Abstract

Type 1 diabetes (T1DM) is associated with increased cardiovascular disease (CVD) and reduced life expectancy. We thus hypothesized that anti-angiogenic miRs are increased in T1DM, and the cardioprotective effect of metformin is mediated via reducing those miRs. In an open label, case-controlled study, 23 T1DM patients without CVD were treated with metformin for eight weeks (TG), matched with nine T1DM patients on standard treatment (SG) and 23 controls (CG). Plasma miR-222, miR-195, miR-21a and miR-126 were assayed by real-time RT-qPCR. The results were correlated with: endothelial function (RHI), circulating endothelial progenitor cells (cEPCs) (vascular repair marker, CD45dimCD34+VEGFR2+ cells) and circulating endothelial cells (cECs) (vascular injury marker, CD45dimCD34+CD133-CD144+ cells). miR-222, miR-195 and miR-21a were higher in T1DM than CG; p = 0.009, p < 0.0001, p = 0.0001, respectively. There was an inverse correlation between logmiR-222 and logRHI (p < 0.05) and a direct correlation between logmiR-222 and logCD34+ (p < 0.05) in TG. Metformin reduced miR-222, miR-195 and miR-21a levels in TG; p = 0.007, p = 0.002 p = 0.0012, respectively. miRs remained unchanged in SG. miR-126 was similar in all groups. There was a positive association between changes in logmiR-222 and logcECs after metformin in TG (p < 0.05). Anti-angiogenic miRs are increased in T1DM. Metformin has cardioprotective effects through downregulating miR-222, miR-195 and miR-21a, beyond improving glycemic control. View Full-Text
Keywords: T1DM; metformin; anti-angiogenic; miRs T1DM; metformin; anti-angiogenic; miRs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ahmed, F.W.; Bakhashab, S.; Bastaman, I.T.; Crossland, R.E.; Glanville, M.; Weaver, J.U. Anti-Angiogenic miR-222, miR-195, and miR-21a Plasma Levels in T1DM Are Improved by Metformin Therapy, Thus Elucidating Its Cardioprotective Effect: The MERIT Study. Int. J. Mol. Sci. 2018, 19, 3242.

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