title: Elevation of miR-221 and -222 in the internal mammary arteries of diabetic subjects and normalization with metformin.
abstract: 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.
authors: Laboratory of Molecular Cardiology, Ochsner Clinic Foundation, New Orleans, LA, United States.
authors: Chasity B
authors: CB
authors: Coleman
authors: Daniel J
authors: DJ
authors: Lightell
authors: Stephanie C
authors: SC
authors: Moss
authors: Michael
authors: M
authors: Bates
authors: Patrick E
authors: PE
authors: Parrino
authors: T Cooper
authors: TC
authors: Woods
mesh_terms: D000368:Aged; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D001026:Coronary Artery Bypass; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008687:Metformin / Q000494:pharmacology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human
references: PLoS One. 2011;6(8):e23925
references: 21887347
references: J Biol Chem. 2009 Feb 6;284(6):3728-38
references: 19088079
references: J Mol Cell Cardiol. 2012 Jan;52(1):245-55
references: 22138289
references: Biochem Biophys Res Commun. 2010 May 28;396(2):359-63
references: 20417618
references: Diabetes Care. 1997 Apr;20(4):627-31
references: 9096992
references: Endocrinology. 2011 Feb;152(2):651-8
references: 21190963
references: Clin Chem. 2013 May;59(5):781-92
references: 23396142
references: Biochem Biophys Res Commun. 2009 Mar 27;381(1):81-3
references: 19351599
references: Diabetologia. 2010 Jun;53(6):1099-109
references: 20198361
references: Atherosclerosis. 2011 Nov;219(1):74-83
references: 21719015
references: Ochsner J. 2007 Fall;7(3):133-6
references: 21603530
references: FASEB J. 2001 Sep;15(11):1989-95
references: 11532979
references: Circ Res. 2009 Feb 27;104(4):476-87
references: 19150885
references: Diabetes. 2005 Jul;54(7):2227-34
references: 15983226
references: J Biol Chem. 2010 Apr 16;285(16):11991-7
references: 20097763
references: Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):611-7
references: 16385087
references: Diabetes. 2003 Oct;52(10):2562-9
references: 14514641
references: Arterioscler Thromb Vasc Biol. 2007 May;27(5):1159-65
references: 17303781
references: Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2388-98
references: 18931034
references: Diabetologia. 2004 Nov;47(11):1906-13
references: 15565373