Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers

Circ J. 2010 Jan;74(1):195-202. doi: 10.1253/circj.cj-09-0345. Epub 2009 Nov 19.


Background: Smoking is a major cardiovascular risk factor, leading to endothelial dysfunction. The present study investigated the hypothesis that pitavastatin, an HMG-CoA reductase inhibitor, may improve endothelial function in chronic smokers via its antioxidant properties.

Methods and results: The 30 male chronic smokers who exhibited mild hypercholesterolemia at the time of physical check-up were enrolled and randomized to the pitavastatin group (2 mg/day, n=15) or the untreated control group (n=15). Before and after the 4-week treatment period, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent dilation by glyceryl trinitrate (GTD) were examined, and the FMD/GTD ratio was calculated. The pitavastatin group showed a significant restoration of endothelial function (percent change in FMD: +49.6% vs +1.4%; percent change in FMD/GTD ratio: +26.6% vs 4.5%, P<0.05 respectively), and a significant reduction in oxidative stress levels (malondialdehyde-low-density lipoprotein-cholesterol: 16.6% vs +7.5%; free radical activity: 1.8% vs +9.7%, P<0.05 respectively) compared with the control group. Pitavastatin had no effect on the number of circulating CD34(+)CD133(+) progenitor cells, endothelial progenitor cells, or the MMP-2, MMP-9 and VEGF levels. In vitro oxidative stress monitoring assay revealed that pitavastatin protected endothelial cells against oxidative stress.

Conclusions: Pitavastatin restores endothelial function, even in chronic smokers, possibly through its antioxidative properties. (Circ J 2010; 74: 195 - 202).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cholesterol / blood
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Free Radicals / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • NADPH Oxidases / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects
  • Quinolines / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Smoking / blood
  • Smoking / physiopathology*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Free Radicals
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • Reactive Oxygen Species
  • Cholesterol
  • Nitric Oxide Synthase Type III
  • NADPH Oxidases
  • pitavastatin