title: The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression.
abstract: METHODS
  Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects.
  
  
  RESULTS
  Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p<0.05) and increased superoxide production (136 ± 5 %, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47(phox) was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment.
  
  
  CONCLUSIONS
  Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47(phox) gene and protein expression.
authors.affiliation: Department of Sports, Health and Exercise Sciences, University of Hull, Hull, UK.|Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Huw S
authors.initials: HS
authors.lastname: Jones
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gordon
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Simba G
authors.initials: SG
authors.lastname: Magwenzi
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Khalid
authors.initials: K
authors.lastname: Naseem
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.|Weill Cornell Medical College Qatar, Doha, Qatar.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Atkin
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, UK.|Campden BRI, Station Road, Chipping Campden, Gloucestershire, UK.
authors.forename: Fraser L
authors.initials: FL
authors.lastname: Courts
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D011794:Quercetin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C
keywords: Endothelial cells; NADPH oxidase; Nitric oxide; Quercetin; Superoxide