Atorvastatin prevents hypoxia-induced inhibition of endothelial nitric oxide synthase expression but does not affect heme oxygenase-1 in human microvascular endothelial cells

Atherosclerosis. 2006 Jul;187(1):26-30. doi: 10.1016/j.atherosclerosis.2006.03.015. Epub 2006 Apr 18.

Abstract

Beneficial cardiovascular effects of statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are particularly assigned to the modulation of inflammation. Endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) are listed among the crucial protective, anti-inflammatory genes in the vasculature. Here we show that atorvastatin at pharmacologically relevant concentration (0.1 microM) enhanced the expression of eNOS in human microvascular endothelial cells (HMEC-1). Moreover, atorvastatin prevented hypoxia-induced decrease in eNOS expression. However, in the same cells atorvastatin was ineffective in modulation of HO-1 protein level. Therefore, we suggest that the protective effect of statins at their pharmacological concentrations is not mediated by enhancement of HO-1 activity, but may involve eNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / metabolism
  • Atorvastatin
  • Blotting, Western
  • Cells, Cultured
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation, Enzymologic*
  • Heme Oxygenase-1 / biosynthesis*
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypercholesterolemia / metabolism
  • Hypoxia*
  • Microcirculation / metabolism
  • Nitric Oxide Synthase Type III / biosynthesis*
  • Pyrroles / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • Nitric Oxide Synthase Type III
  • Heme Oxygenase-1