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 journalArticle

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

Fingerprint

coenzyme Q10
Endothelial cells
Lipopolysaccharides
Human Umbilical Vein Endothelial Cells
Anti-Inflammatory Agents
Endothelial Cells
Modulation
Interleukin-6
Interleukin-1 Receptor-Associated Kinases
Phenotype
Curbs
Cell Aging
Biomarkers
Stem cells
Protein Kinases
Blood Vessels
Stem Cells
Antioxidants
Aging of materials
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation. / Olivieri, Fabiola; Lazzarini, Raffaella; Babini, Lucia; Prattichizzo, Francesco; Rippo, Maria Rita; Tiano, Luca; Di Nuzzo, Silvia; Graciotti, Laura; Festa, Roberto; Brugè, Francesca; Orlando, Patrick; Silvestri, Sonia; Capri, Miriam; Palma, Linda; Magnani, Mauro; Franceschi, Claudio; Littarru, Gian Paolo; Procopio, Antonio Domenico.

In: Free Radical Biology and Medicine, Vol. 63, 2013, p. 410-420.

Research output: Contribution to journalArticle

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 2013, 'Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation', Free Radical Biology and Medicine, vol. 63, pp. 410-420. https://doi.org/10.1016/j.freeradbiomed.2013.05.033
Olivieri, Fabiola ; Lazzarini, Raffaella ; Babini, Lucia ; Prattichizzo, Francesco ; Rippo, Maria Rita ; Tiano, Luca ; Di Nuzzo, Silvia ; Graciotti, Laura ; Festa, Roberto ; Brugè, Francesca ; Orlando, Patrick ; Silvestri, Sonia ; Capri, Miriam ; Palma, Linda ; Magnani, Mauro ; Franceschi, Claudio ; Littarru, Gian Paolo ; Procopio, Antonio Domenico. / Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation. In: Free Radical Biology and Medicine. 2013 ; Vol. 63. pp. 410-420.
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AU - Olivieri, Fabiola

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AU - Prattichizzo, Francesco

AU - Rippo, Maria Rita

AU - Tiano, Luca

AU - Di Nuzzo, Silvia

AU - Graciotti, Laura

AU - Festa, Roberto

AU - Brugè, Francesca

AU - Orlando, Patrick

AU - Silvestri, Sonia

AU - Capri, Miriam

AU - Palma, Linda

AU - Magnani, Mauro

AU - Franceschi, Claudio

AU - Littarru, Gian Paolo

AU - Procopio, Antonio Domenico

PY - 2013

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N2 - 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.

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