title: Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients.
abstract: BACKGROUND
  Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91(phox), but the underlying mechanism is still undefined.
  
  
  OBJECTIVE
  To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin.
  
  
  RESULTS
  We compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91(phox) serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91(phox), urinary isoprostanes and platelet oxygen free radicals (p<0.001). In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47(phox) translocation to gp91(phox) and soluble gp91(phox) cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation.
  
  
  CONCLUSIONS
  This study provides the first evidence that in patients higher APN serum levels are associated with gp91(phox) down-regulation. APN-mediated gp91(phox) reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect.
authors.affiliation: Prima Clinica Medica-University of Rome La Sapienza, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Serena
authors.initials: S
authors.lastname: Di Santo
authors.forename: Simona
authors.initials: S
authors.lastname: Bartimoccia
authors.forename: Valerio
authors.initials: V
authors.lastname: Sanguigni
authors.forename: Laura
authors.initials: L
authors.lastname: Napoleone
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tanzilli
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D000069059:Atorvastatin; D001792:Blood Platelets / Q000201:enzymology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005609:Free Radicals; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D000975:Antioxidants; D005609:Free Radicals; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008562:Membrane Glycoproteins; D011758:Pyrroles; D000069059:Atorvastatin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases