title: Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation.
abstract: Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H₂), 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 CoQ10H₂ 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-κB activation diminished after CoQ10H₂ pretreatment in both 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.
authors.affiliation: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60020 Ancona, Italy. f.olivieri@univpm.it
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lazzarini
authors.forename: Lucia
authors.initials: L
authors.lastname: Babini
authors.forename: Francesco
authors.initials: F
authors.lastname: Prattichizzo
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rippo
authors.forename: Luca
authors.initials: L
authors.lastname: Tiano
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Nuzzo
authors.forename: Laura
authors.initials: L
authors.lastname: Graciotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Festa
authors.forename: Francesca
authors.initials: F
authors.lastname: Brugè
authors.forename: Patrick
authors.initials: P
authors.lastname: Orlando
authors.forename: Sonia
authors.initials: S
authors.lastname: Silvestri
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.forename: Linda
authors.initials: L
authors.lastname: Palma
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Littarru
authors.forename: Antonio Domenico
authors.initials: AD
authors.lastname: Procopio
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D014451:Ubiquinone; C026663:ubiquinol-10; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: Coenzyme Q10; Free radicals; HUVEC; IL-6; Replicative senescence; SASP; miR-146a