Research Paper Volume 6, Issue 9 pp 771—786
Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells
- 1 Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
- 2 Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy
- 3 Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy
- 4 CNR, National Research Council of Italy, Institute for Molecular Genetics, Unit of Bologna IOR, Bologna, Italy
- 5 Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy
- 6 Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy
- 7 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- 8 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
- 9 Clinical & Molecular Diagnostic Laboratory, INRCA-IRCCS National Institute, Ancona, Italy
- 10 Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- 11 Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy
- 12 Department of Dentistry and Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy
- 13 Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni, Italy
- 14 C.I.G. Interdepartmental Center "L. Galvani", University of Bologna, Bologna, Italy
- 15 Experimental Models in Clinical Pathology, INRCA-IRCCS National Institute, Ancona, Italy
Received: June 18, 2014 Accepted: October 5, 2014 Published: October 7, 2014
https://doi.org/10.18632/aging.100693How to Cite
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.