Elevation of miR-221 and -222 in the internal mammary arteries of diabetic subjects and normalization with metformin

• Published in: Molecular and cellular endocrinology Vol. 374; no. 1-2; pp. 125 - 129
• Main Authors: Coleman, Chasity B., Lightell, Daniel J., Moss, Stephanie C., Bates, Michael, Parrino, Patrick E., Woods, T. Cooper
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15.07.2013
• Subjects: Aged; Biopsy; cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Cardiovascular Diseases - surgery; Coronary Artery Bypass; coronary vessels; Cross-Sectional Studies; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - surgery; Female; Gene Expression Regulation; Humans; Hypoglycemic Agents - pharmacology; Internal mammary artery; Male; Mammary Arteries - metabolism; Mammary Arteries - pathology; Mammary Arteries - surgery; messenger RNA; Metformin; Metformin - pharmacology; microRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-221/222; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Primary Cell Culture; risk factors; smooth muscle; Vascular smooth muscle cell; CVD; AMPK; Vascular smooth muscle cell; VSMC; Diabetes; Metformin; Internal mammary artery; IMA; miR-221/222
• DOI: 10.1016/j.mce.2013.04.019
• ISSN: 0303-7207; 1872-8057

•miR-221/222 accelerate cell proliferation and intimal thickening.•miR-221/222 are elevated in the internal mammary arteries of diabetic subjects.•Diabetic subjects on metformin therapy exhibit normal miR-221/222 levels. 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, p27Kip1, 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 p27Kip1 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.