title: Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells.
abstract: Circulating miR-126-3p levels were determined in 136 healthy subjects (CTRs) aged 20-90 years and 193 patients with type-2 diabetes mellitus (T2DMs) aged 40-80 years, to explore the combined effect of age and glycemic state on miR-126-3p expression. Moreover, intra/extracellular miR-126-3p levels were measured in human endothelial cells (HUVECs) undergoing senescence under normo/hyper-glycemic conditions. Plasma miR-126-3p was significantly higher in the oldest compared with the youngest CTRs ( <45 vs. >75 years; relative expression: 0.27±0.29 vs. 0.48±0.39, p=0.047). Age-based comparison between CTRs and T2DM demonstrated significantly different miR-126-3p levels only in the oldest (0.48±0.39 vs. 0.22±0.23, p<0.005). After multiple adjustments, miR-126-3p levels were seen to be lower in patients with poor glycemic control, compared with age-matched CTRs. The age-related increase in plasma miR-126-3p found in CTRs was paralleled by a 5/6-fold increase in intra/extracellular miR-126-3p in in vitro-cultured HUVECs undergoing senescence. Notably, significant down- regulation of SPRED-1 protein, a validated miR-126-3p target, was found in senescent HUVECs. Moreover, miR-126-3p expression was down-regulated in intermediate-age HUVECs grown in high-glucose medium until senescence. Aging/senescence-associated miR-126-3p up-regulation is likely a senescence-associated compensatory mechanism that is blunted when endothelial cells are exposed to high glucose levels, a phenomenon that probably occurs in vivo in T2DM patients.
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy. Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy. CNR, National Research Council of Italy, Institute for Molecular Genetics, Unit of Bologna IOR, Bologna, Italy. Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafè
authors.affiliation: Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Spazzafumo
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Gobbi
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Prattichizzo
authors.affiliation: Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Rina
authors.initials: R
authors.lastname: Recchioni
authors.affiliation: Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Marcheselli
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: La Sala
authors.affiliation: Clinical and Molecular Diagnostic Laboratory, INRCA-IRCCS National Institute, Ancona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rippo
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fulgenzi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lazzarini
authors.affiliation: Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bonfigli
authors.affiliation: Department of Dentistry and Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Brugè
authors.affiliation: Department of Dentistry and Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tiano
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Genovese
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.affiliation: Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Boemi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy. C.I.G. Interdepartmental Center "L. Galvani", University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy. Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Antonio Domenico
authors.initials: AD
authors.lastname: Procopio
authors.affiliation: Experimental Models in Clinical Pathology, INRCA-IRCCS National Institute, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Testa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D055815:Young Adult
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs