RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .
Simvastatin Modulates Expression of the PON1 Gene and Increases Serum Paraoxonase: A Role for Sterol Regulatory Element–Binding Protein-2
Background —The HDL-associated enzyme paraoxonase protects LDLs from oxidative stress . 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) appear to favorably influence the atherosclerotic process by different mechanisms . The present study examined the influence of simvastatin on paraoxonase expression and serum paraoxonase levels . Methods and Results —Simvastatin upregulated in a dose-dependent manner the activity of the promoter of the paraoxonase gene in expression cassettes transfected into HepG2 cells . Upregulation could be blocked by mevalonate and other intermediates of the cholesterol biosynthetic pathway . Simvastatin increased nuclear factors , notably sterol regulatory element – binding protein-2 , capable of binding to the paraoxonase promoter ; this was also blocked by mevalonate . Sterol regulatory element – binding protein-2 upregulated promoter activity in vitro . Patients treated with statin  showed a significant increase in serum concentrations and activities of paraoxonase . Conclusions —The data indicate that simvastatin can modulate expression in vitro of the antioxidant enzyme paraoxonase and is associated with increased serum paraoxonase concentration and activity . It is consistent with effects of simvastatin treatment , which have the potential to influence beneficially antiatherogenic mechanisms at the HDL level . The study provides evidence for 1 molecular mechanism by which paraoxonase gene expression could be regulated
RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .