Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 374, Issue 1-2, Pages 125-129Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.04.019
Keywords
miR-221/222; Diabetes; Metformin; Internal mammary artery; Vascular smooth muscle cell
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Funding
- National Center for Research Resources [P20 RR018766]
- National Institute of General Medical Sciences [P20 GM103514, P30 GM103337]
- National Institutes of Health and Basic Science [1-13-BS-210]
- American Diabetes Association
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Diabetes is a major risk factor for cardiovascular disease and is associated with increased intimal thickening and accelerated vascular smooth muscle cell (VSMC) proliferation. We measured the expression of two microRNAs that promote intimal thickening, miR-221/222, and mRNA encoding a downstream target, p27(Kip1), in internal mammary artery (IMA) segments collected from 37 subjects undergoing coronary artery bypass grafting. The segments were stratified into three groups: non-diabetic subjects (ND), diabetic subjects not on metformin (DMMet-), and diabetic subjects on metformin (DMMet+). The DMMet- group exhibited a significant increase in miR-221/222 and decrease in p27(KiP1) mRNA compared to both the ND and DMMet+ groups. miR-221/222 levels inversely correlated with metformin dose. VSMCs isolated from the IMAs of the DMMet- group proliferate at a faster rate than those of the ND and DMMet+ groups. Further studies into the importance of miR-221/222 in the increased intimal thickening observed in diabetic subjects is warranted. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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