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

作者：Olivieri Fabiola^*; Bonafe 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; Bruge Francesca; Tiano Luca; Genovese Stefano; Ceriello Antonio; Boemi Massimo; Franceschi Claudio; Procopio Antonio Domenico; Testa Roberto

来源：Aging-US, 2014, 6(9): 771-787.

DOI：10.18632/aging.100693

• miR-126-3p
• T2DM
• HUVEC
• senescence

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.

• 出版日期2014-9