Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Aging (Albany, NY.), 2014-10, Vol.6 (9), p.771-786

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.