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Article

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

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. https://doi.org/10.3390/ijms19103242

AMA Style

Ahmed FW, Bakhashab S, Bastaman IT, Crossland RE, Glanville M, Weaver JU. 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. International Journal of Molecular Sciences. 2018; 19(10):3242. https://doi.org/10.3390/ijms19103242

Chicago/Turabian Style

Ahmed, Fahad W., Sherin Bakhashab, Inda T. Bastaman, Rachel E. Crossland, Michael Glanville, and Jolanta U. Weaver. 2018. "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" International Journal of Molecular Sciences 19, no. 10: 3242. https://doi.org/10.3390/ijms19103242

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