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Research Paper|Volume 6, Issue 9|pp 771—786

Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells

Fabiola Olivieri1,2, Massimiliano Bonafè3,4,5, Liana Spazzafumo6, Mirko Gobbi1, Francesco Prattichizzo1, Rina Recchioni2, Fiorella Marcheselli2, Lucia La Sala7,8, Roberta Galeazzi9, Maria Rita Rippo1, Gianluca Fulgenzi1, Sabrina Angelini10, Raffaella Lazzarini1, Anna Rita Bonfigli11, Francesca Brugè12, Luca Tiano12, Stefano Genovese13, Antonio Ceriello7,8, Massimo Boemi11, Claudio Franceschi3,14, Antonio Domenico Procopio1,2, Roberto Testa15
  • 1Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
  • 2Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy
  • 3Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy
  • 4CNR, National Research Council of Italy, Institute for Molecular Genetics, Unit of Bologna IOR, Bologna, Italy
  • 5Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy
  • 6Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy
  • 7Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  • 8Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
  • 9Clinical & Molecular Diagnostic Laboratory, INRCA-IRCCS National Institute, Ancona, Italy
  • 10Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
  • 11Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy
  • 12Department of Dentistry and Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy
  • 13Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni, Italy
  • 14C.I.G. Interdepartmental Center "L. Galvani", University of Bologna, Bologna, Italy
  • 15Experimental Models in Clinical Pathology, INRCA-IRCCS National Institute, Ancona, Italy

* * Equal contribution

Received: June 18, 2014Accepted: October 5, 2014Published: October 7, 2014
https://doi.org/10.18632/aging.100693

Copyright: © 2014 Olivieri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.