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Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic

Roberto Carnevale1, Pasquale Pignatelli, Serena Di Santo

  • 1Prima Clinica Medica-University of Rome La Sapienza, Rome, Italy.

Atherosclerosis
|September 14, 2010
PubMed
Abstract

Insights

Atorvastatin treatment increased adiponectin (APN) levels, which were linked to reduced oxidative stress markers like sgp91(phox). This suggests APN mediates atorvastatin's antioxidant effects by down-regulating NADPH oxidase activity.

Area of Science:

  • Cardiovascular Research
  • Biochemistry
  • Pharmacology

Background:

  • Atorvastatin reduces NADPH oxidase (sgp91(phox)) levels, but the mechanism remains unclear.
  • Oxidative stress is implicated in cardiovascular disease pathogenesis.

Purpose of the Study:

  • To investigate if adiponectin (APN) mediates the inhibitory effects of atorvastatin on oxidative stress.
  • To explore the relationship between APN, sgp91(phox), and oxidative stress markers.

Main Methods:

  • Comparative study of hypercholesterolemic patients and healthy subjects.
  • Randomized trial of low-fat diet versus diet plus atorvastatin (10 mg/day) for 30 days.
  • In vitro experiments assessing APN's effect on NADPH oxidase subunit translocation and cleavage.

Main Results:

  • Hypercholesterolemic patients had lower APN and higher oxidative stress markers (sgp91(phox), isoprostanes, free radicals).
  • Atorvastatin treatment increased APN levels, which inversely correlated with reduced sgp91(phox) and oxidative stress markers (p<0.001).
  • In vitro, APN (5-10 ng/ml) inhibited NADPH oxidase assembly and activation.

Conclusions:

  • Higher serum APN levels are associated with reduced gp91(phox) in patients.
  • Adiponectin-mediated reduction of gp91(phox) is a potential mechanism for atorvastatin's antioxidant effect.

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