HMG-CoA reductase inhibitors reduce interleukin-6 synthesis in human vascular smooth muscle cells

Cardiovasc Drugs Ther. 2002 Mar;16(2):121-6. doi: 10.1023/a:1015701415588.

Abstract

Interleukin-6 (IL-6) is a key molecule in chronic inflammation and has been implicated in the progression of atherosclerosis. HMG-CoA reductase inhibitors (statins) may reduce the cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid as well as lipid-lowering mechanisms, but their anti-inflammatory effects on the vascular tissue have not been fully elucidated. We investigated the effects of fluvastatin on IL-6 synthesis in human vascular smooth muscle cells (VSMCs). Addition of fluvastatin decreased IL-6 synthesis in VSMCs in a time (0-24 hours)- and dose (10(-8)-10(-5) mol/L)-dependent manner. Fluvastatin also decreased IL-6 mRNA expression in VSMCs. The effects of fluvastatin on IL-6 expression were completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not squalene. Inhibition of Rho by C3 exoenzyme or Rho kinase by Y-27632 significantly decreased IL-6 expression in VSMCs. In conclusion, fluvastatin decreases IL-6 synthesis in human VSMCs through inhibition of Rho pathway. These findings suggested that reduction of IL-6 expression by statins may partially explain their therapeutic effects in patients with coronary artery disease.

Publication types

  • Comparative Study

MeSH terms

  • ADP Ribose Transferases / metabolism
  • Amides / pharmacology
  • Analysis of Variance
  • Animals
  • Botulinum Toxins / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Indoles / pharmacology*
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Intracellular Signaling Peptides and Proteins
  • Lovastatin / pharmacology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Pravastatin / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Pyridines / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • rho-Associated Kinases

Substances

  • Amides
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • RNA, Messenger
  • Y 27632
  • Fluvastatin
  • Lovastatin
  • cerivastatin
  • ADP Ribose Transferases
  • exoenzyme C3, Clostridium botulinum
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • Botulinum Toxins
  • Pravastatin