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

Fabiola Olivieri; Massimiliano Bonafè; Liana Spazzafumo; Mirko Gobbi; Francesco Prattichizzo; Rina Recchioni; Fiorella Marcheselli; Lucia La Sala; Roberta Galeazzi; Maria Rita Rippo; Gianluca Fulgenzi; Sabrina Angelini; Raffaella Lazzarini; Anna Rita Bonfigli; Francesca Brugè; Luca Tiano; Stefano Genovese; Antonio Ceriello; Massimo Boemi; Claudio Franceschi; Antonio Domenico Procopio; Roberto Testa

doi:doi:10.18632/aging.100693

Research Paper Volume 6, Issue 9 pp 771—786

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

Fabiola Olivieri^{1,2,

,}, Massimiliano Bonafè^{3,4,5,

,}, Liana Spazzafumo^6,, Mirko Gobbi^1,, Francesco Prattichizzo^1,, Rina Recchioni^2,, Fiorella Marcheselli^2,, Lucia La Sala^7,8,, Roberta Galeazzi^9,, Maria Rita Rippo^1,, Gianluca Fulgenzi^1,, Sabrina Angelini^10,, Raffaella Lazzarini^1,, Anna Rita Bonfigli^11,, Francesca Brugè^12,, Luca Tiano^12,, Stefano Genovese^13,, Antonio Ceriello^7,8,, Massimo Boemi^11,, Claudio Franceschi^3,14,, Antonio Domenico Procopio^1,2,, Roberto Testa^15,,

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

* Equal contribution

Received: June 18, 2014 Accepted: October 5, 2014 Published: October 7, 2014

https://doi.org/10.18632/aging.100693
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Olivieri F, Bonafè M, Spazzafumo L, Gobbi M, Prattichizzo F, Recchioni R, Marcheselli F, Sala LL, Galeazzi R, Rippo MR, Fulgenzi G, Angelini S, Lazzarini R, et al, . Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells. Aging (Albany NY). 2014; 6:771-786. https://doi.org/10.18632/aging.100693

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Provider: 
        TY  - JOUR
        AU  - Olivieri, Fabiola 
        AU  - Bonafè, Massimiliano 
        AU  - Spazzafumo, Liana 
        AU  - Gobbi, Mirko 
        AU  - Prattichizzo, Francesco 
        AU  - Recchioni, Rina 
        AU  - Marcheselli, Fiorella 
        AU  - Sala, Lucia La 
        AU  - Galeazzi, Roberta 
        AU  - Rippo, Maria Rita 
        AU  - Fulgenzi, Gianluca 
        AU  - Angelini, Sabrina 
        AU  - Lazzarini, Raffaella 
        AU  - Bonfigli, Anna Rita 
        AU  - Brugè, Francesca 
        AU  - Tiano, Luca 
        AU  - Genovese, Stefano 
        AU  - Ceriello, Antonio 
        AU  - Boemi, Massimo 
        AU  - Franceschi, Claudio 
        AU  - Procopio, Antonio Domenico 
        AU  - Testa, Roberto 
        TI  - Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 6
        IS  - 9
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.100693
        DO  - 10.18632/aging.100693
        SP  - 771
        EP  - 786
        PY  - 
        AB  - 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 (&lt;45 vs. &gt;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&lt;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.
        ER  -

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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.

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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

Received: June 18, 2014 Accepted: October 5, 2014 Published: October 7, 2014

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