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

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

Research output: Contribution to journalArticlepeer-review

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 CoQ10H 2 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.

Original languageEnglish
Pages (from-to)410-420
Number of pages11
JournalFree Radical Biology and Medicine
Volume63
DOIs
Publication statusPublished - 2013

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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