Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients.
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.
Carnevale
Roberto
R
Prima Clinica Medica-University of Rome La Sapienza, Rome, Italy.
Pignatelli
Pasquale
P
Di Santo
Serena
S
Bartimoccia
Simona
S
Sanguigni
Valerio
V
Napoleone
Laura
L
Tanzilli
Gaetano
G
Basili
Stefania
S
Violi
Francesco
F
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*
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