Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia.
OBJECTIVE
The inhibition of oxidative stress is among the most relevant pleiotropic effects of statins. The mechanism by which statins exert their antioxidant effect in vivo is still undefined. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. Methods/Results- We developed an ELISA to evaluate serum levels of soluble-gp91(phox), the catalytic core of phagocyte NADPH oxidase. In a cross-sectional study performed in 30 hypercholesterolemic patients and in 20 controls, serum soluble-gp91(phox) and urinary isoprostane, a marker of oxidative stress, were measured. The 2 variables were also measured in hypercholesterolemic patients, randomized to diet (n=15), or diet plus atorvastatin (10 mg daily, n=15) and followed for 30 days. Compared to controls, hypercholesterolemic patients had higher and significantly correlated (R=0.71; P<0.001) serum soluble-gp91(phox) (P<0.001) and urinary isoprostanes (P<0.001). After follow-up, the statin-allocated group showed a significant reduction of soluble-gp91(phox) (-33%, P<0.01), that paralleled that of isoprostanes (-37%, P<0.01) and cholesterol (-25%, P<0.01). The diet-allocated group showed only a weak reduction of cholesterol.


CONCLUSIONS
Our study demonstrates that statins exert an antioxidant effect via inhibition of soluble gp91(phox) expression.
Pignatelli
Pasquale
P
Department of Experimental Medicine, Divisione I Clinica Medica, Sapienza University, Rome, Italy.
Carnevale
Roberto
R
Cangemi
Roberto
R
Loffredo
Lorenzo
L
Sanguigni
Valerio
V
Stefanutti
Claudio
C
Basili
Stefania
S
Violi
Francesco
F
D000975:Antioxidants / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001792:Blood Platelets / Q000201:enzymology; D015153:Blotting, Western; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy* / Q000201:enzymology*; D047468:Immunoprecipitation; D028421:Isoprostanes / Q000652:urine; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood*; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000975:Antioxidants; D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D028421:Isoprostanes; D008562:Membrane Glycoproteins; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases