Premium
Simvastatin Increases Endothelial Nitric Oxide Synthase Expression in Cultured Endothelial Cells Preconditioned with Steady Laminar Flow
Author(s) -
Rossi Joanna,
Rouleau Léonie,
Tardif JeanClaude,
Leask Richard L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.311.2
Subject(s) - enos , simvastatin , nitric oxide synthase , reductase , chemistry , statin , hmg coa reductase , hydroxymethylglutaryl coa reductase , medicine , nitric oxide , endothelium , endocrinology , biology , pharmacology , biochemistry , enzyme
Statins (HMG‐CoA reductase inhibitors) are known to have benefits in vascular biology beyond lipid reduction. It has been reported that statins can elevate the expression of endothelial nitric oxide synthase (eNOS) in cultured endothelial cells; however, it is not known whether this increase is conserved under hemodynamic stimulation. Methods and Results Human abdominal aortic endothelial cells were pre‐conditioned with fluid shear stress (1, 10 or 20 dynes/cm 2 ) for 6 h. Without stopping the perfusion, control vehicle, simvastatin or simvastatin with mevalonate were added to the perfusion media and the flow experiment was continued for 24 h. As expected, eNOS mRNA and protein increased with increasing levels of fluid shear stress. Treatment with 1 or 10 µM of simvastatin further elevated eNOS mRNA and protein. Co‐incubation with mevalonate, a precursor to cholesterol synthesis, eliminated the effect of the statin, but had no effect on shear induction of eNOS. This suggests that the effect of statins on eNOS expression is conserved under flow and that the mechanism in which simvastatin induces eNOS is through inhibition of HMG‐CoA reductase. Conclusions Simvastatin enhances eNOS expression in cultured endothelial cells pre‐conditioned with steady laminar flow through inhibition of HMG‐CoA reductase. These results may explain the benefits of statins in the clinic beyond lipid reduction.