Regulation of endothelial nitric oxide synthase and endothelin-1 expression by fluvastatin in human vascular endothelial cells

Jpn J Pharmacol. 2001 Feb;85(2):147-54. doi: 10.1254/jjp.85.147.

Abstract

We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on endothelial vasoactive substances using human umbilical vein endothelial cells (HUVECs). Incubation of HUVECs with fluvastatin for 12 h increased endothelial nitric oxide synthase (eNOS) mRNA expression in a concentration-dependent manner (peak, 276 +/- 38%, mean +/- S.D., of the control, at 1.0 microM fluvastatin, P<0.01). In addition, fluvastatin increased eNOS protein production (245 +/- 51% of the control level, P<0.05) as well as nitrite production (165 +/- 35% of the control level, P<0.01). In contrast, incubation of HUVECs with 1.0 microM fluvastatin for 12 h significantly reduced the production of endothelin-1 (ET-1) and preproET-1 mRNA expression in HUVECs (28 +/- 1% and 39 +/- 1% of the control level, respectively, P<0.01). Our results suggest that fluvastatin might be involved in improvement of endothelial function and prevention of the progression of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • DNA Primers
  • Endothelin-1 / biosynthesis
  • Endothelin-1 / drug effects*
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fluvastatin
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Indoles / pharmacology*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Nitrites / metabolism
  • RNA, Messenger / genetics

Substances

  • DNA Primers
  • Endothelin-1
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Nitrites
  • RNA, Messenger
  • Fluvastatin
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III