title: Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes.
abstract: Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The current study focuses on the role of circulating miRNAs in patients with type 1 diabetes and their association with diabetic retinopathy. A total of 29 miRNAs were quantified in serum samples (n = 300) using a nested case-control study design in two prospective cohorts of the DIabetic REtinopathy Candesartan Trial (DIRECT): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with nonproliferative retinopathy at baseline. Two miRNAs previously implicated in angiogenesis, miR-27b and miR-320a, were associated with incidence and with progression of retinopathy: the odds ratio per SD higher miR-27b was 0.57 (95% CI 0.40, 0.82; P = 0.002) in PREVENT-1, 0.78 (0.57, 1.07; P = 0.124) in PROTECT-1, and 0.67 (0.50, 0.92; P = 0.012) combined. The respective odds ratios for higher miR-320a were 1.57 (1.07, 2.31; P = 0.020), 1.43 (1.05, 1.94; P = 0.021), and 1.48 (1.17, 1.88; P = 0.001). Proteomics analyses in endothelial cells returned the antiangiogenic protein thrombospondin-1 as a common target of both miRNAs. Our study identifies two angiogenic miRNAs, miR-320a and miR-27b, as potential biomarkers for diabetic retinopathy.
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
authors.forename: Anna
authors.initials: A
authors.lastname: Zampetaki
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K. Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
authors.forename: Simon
authors.initials: S
authors.lastname: Burr
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Langley
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Steno Diabetes Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Institute of Cardiovascular Science, University College London, London, U.K. n.chaturvedi@ucl.ac.uk manuel.mayr@kcl.ac.uk.
authors.forename: Nishi
authors.initials: N
authors.lastname: Chaturvedi
authors.affiliation: King's British Heart Foundation Centre of Research Excellence, King's College London, London, U.K. n.chaturvedi@ucl.ac.uk manuel.mayr@kcl.ac.uk.
authors.forename: Manuel
authors.identifier: http://orcid.org/0000-0002-0597-829X
authors.initials: M
authors.lastname: Mayr
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics*; D016017:Odds Ratio; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C531388:MIRN27 microRNA, human; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D019700:Thrombospondin 1