title: Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy.
abstract: Microangiopathy due to endothelial dysfunction is a major contributing factor to the development of diabetes-induced cardiovascular disease (CVD). Dysregulation of endothelial-specific microRNAs (miRs) is correlated with impaired angiogenesis and cell survival. We investigated the profile of two angiomiRs, miR-126, and miR-132, in the plasma of type 2 diabetic individuals without any known history of CVD as well as in the cardiac tissues collected from diabetics undergoing cardiac surgery.
  
  
  
  The presence of diabetes alone significantly decreased both angiomiRs in the plasma and the myocardium. The down-regulation of angiomiRs was also associated with reduced capillaries and arterioles and increased endothelial cell apoptosis, the hallmark of microangiopathy. Importantly, a time course study in a type 2 diabetic mouse model confirmed that the down-regulation of angiomiRs preceded endothelial apoptosis as well as alterations in the density of the microvasculature. Finally, therapeutic overexpression of both angiomiRs in diabetic aortic rings and human umbilical vein endothelial cells exposed to high glucose (HG) abrogated the deleterious effects of diabetes and HG on cell survival and proliferation and restored their angiogenic potential.
  
  
  
  These novel findings demonstrate that the down-regulation of angiomiRs is a major underlying mechanism for the development of microangiopathy in diabetic hearts. Therefore, therapeutic restoration of angiomiRs could become a potential approach to combat the cardiovascular complications of diabetes.
authors.affiliation: Department of Physiology-HeartOtago, Otago School of Medical Sciences.
authors.forename: Shruti
authors.initials: S
authors.lastname: Rawal
authors.affiliation: Department of Physiology-HeartOtago, Otago School of Medical Sciences.
authors.forename: Pujika Emani
authors.initials: PE
authors.lastname: Munasinghe
authors.affiliation: Department of Physiology-HeartOtago, Otago School of Medical Sciences.
authors.forename: Amol
authors.initials: A
authors.lastname: Shindikar
authors.affiliation: Department of Physiology-HeartOtago, Otago School of Medical Sciences.
authors.forename: Jono
authors.initials: J
authors.lastname: Paulin
authors.affiliation: Christchurch Heart Institute, University of Otago.
authors.forename: Vicky
authors.initials: V
authors.lastname: Cameron
authors.affiliation: Departments of Medicine.
authors.forename: Patrick
authors.initials: P
authors.lastname: Manning
authors.affiliation: Medicine-Cardiology.
authors.forename: Michael J A
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Surgery.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Jones
authors.affiliation: Cardiothoracic Surgery, Dunedin School of Medicine, University of Otago.
authors.forename: Richard
authors.initials: R
authors.lastname: Bunton
authors.affiliation: Cardiothoracic Surgery, Dunedin School of Medicine, University of Otago.
authors.forename: Ivor
authors.initials: I
authors.lastname: Galvin
authors.affiliation: Department of Physiology-HeartOtago, Otago School of Medical Sciences; rajesh.katare@otago.ac.nz.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Katare
mesh_terms: D000818:Animals; D017209:Apoptosis; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection
chemical_list: C527111:MIRN126 microRNA, human; C545201:MIRN126 microRNA, mouse; C547077:MIRN132 microRNA, human; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs
keywords: Cardiac microangiopathy ; Diabetes ; MicroRNAs ; Vascular dysfunction