Clinical evidence demonstrates that ubiquinol-10, the reduced active form of Coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and likely 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 (HUVEC). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVEC, used as a model of vascular aging, during replicative senescence in absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVEC had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment both in young and senescent cells. However, short-term CoQ10H2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 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 CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 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.
Olivieri F, Lazzarini R, Babini L, Prattichizzo F, Rippo MR, Tiano L, Di Nuzzo S, Graciotti L, Festa R, Brugè F, Orlando P, Silvestri S, Capri M, Palma L, Magnani M, Franceschi C, Littarru GP, Procopio AD. Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation. Free Radic Biol Med. 2013 May Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy