Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation

作者：Olivieri Fabiola^*; Lazzarini Raffaella; Babini Lucia; Prattichizzo Francesco; Rippo Maria Rita; Tiano Luca; Di Nuzzo Silvia; Graciotti Laura; Festa Roberto; Bruge Francesca; Orlando Patrick; Silvestri Sonia; Capri Miriam; Palma Linda; Magnani Mauro; Franceschi Claudio; Littarru Gian Paolo; Procopio Antonio Domenico

来源：Free Radical Biology and Medicine, 2013, 63: 410-420.

DOI：10.1016/j.freeradbiomed.2013.05.033

• miR-146a
• Replicative senescence
• HUVEC
• Coenzyme Q10
• SASP
• IL-6
• Free radicals

Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H(2)), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H(2) supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-kappa B activation diminished after CoQ10H(2) pretreatment in both young and senescent cells. However, short-term CoQ10H(2) supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H(2) supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H(2) incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H(2) stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.

• 出版日期2013-10