title: A novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathways.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disease of the vessel wall associated with oxidized low-density lipoprotein (oxLDL)-induced apoptosis of endothelial cells. Coenzyme Q10 (CoQ10), a potent antioxidant and a critical intermediate of the electron transport chain, has been reported to inhibit LDL oxidation and thus the progression of atherosclerosis. However, its molecular mechanisms on endothelial cells remain still unclarified.
  
  
  METHODS
  In this study, primary human umbilical vein endothelial cell cultures treated with oxLDL were used to explore the protective effects of CoQ10.
  
  
  RESULTS
  Our results showed that CoQ10 attenuated the oxLDL-induced generation of reactive oxygen species and improved the antioxidant capacity. CoQ10 also attenuated the oxLDL-mediated down-regulation of endothelial nitric oxide synthase (eNOS) and up-regulation of inducible nitric oxide synthase (iNOS). In addition, CoQ10 suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, release of proinflammatory cytokines and the adherence of monocytic THP-1 cells. Moreover, CoQ10 attenuated oxLDL-altered proapoptotic responses. The inhibitor of eNOS (L-NIO 10 μM) and iNOS (1400W 10 μM) as well as NO enhancer (SNP 10 μM) were used to clean up the mechanism.
  
  
  CONCLUSIONS
  These results provide new insight into the possible molecular mechanisms by which CoQ10 protects against atherogenesis by NO-related pathways.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Chung-Lan
authors.initials: CL
authors.lastname: Kao
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Yang
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.forename: Hsiang-Yun
authors.initials: HY
authors.lastname: Chou
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Chen
authors.forename: Guang-Yuh
authors.initials: GY
authors.lastname: Chiou
authors.forename: Li-Hsin
authors.initials: LH
authors.lastname: Chen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Yang
authors.forename: Tsan-Hung
authors.initials: TH
authors.lastname: Chiu
authors.forename: Chiou-Sheng
authors.initials: CS
authors.lastname: Tsai
authors.forename: Hsiu-Chung
authors.initials: HC
authors.lastname: Ou
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D017209:Apoptosis; D004249:DNA Damage; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D014815:Vitamins; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C024989:coenzyme Q10