Simvastatin inhibits the migration and adhesion of monocytic cells and disorganizes the cytoskeleton of activated endothelial cells

Eur J Pharmacol. 2006 Oct 24;548(1-3):53-63. doi: 10.1016/j.ejphar.2006.08.003. Epub 2006 Aug 15.


Statins are powerful agents for lowering plasma cholesterol levels, which act by inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase. Evidence suggests that some of the beneficial effects may depend on their anti-inflammatory properties, due to their ability to suppress the synthesis of isoprenoids. The present study analyzes the effects of short-term simvastatin exposure on monocyte migration, cell adhesion, and endothelial cytoskeleton. We demonstrate that simvastatin completely inhibited the migration of THP-1 monocytic cells after 24 h of incubation, being prevented by coincubation with mevalonate (MVA) and geranylgeranylpyrophosphate (GGPP), but not by farnesylpyrophosphate (FPP). Simvastatin decreased chemotaxis to 70% after one hour of incubation; surprisingly neither MVA, GGPP nor FPP were able to restore the effects of the drug. Simvastatin also significantly reduced the adhesion of monocytes to interleukin-1beta (IL-1beta)-activated endothelium to 80% after preincubation for 24 h. This effect was completely reversed by coincubation with MVA and GGPP, and partially with FPP. Unexpectedly, simvastatin increased adhesion molecules expression VCAM-1 and ICAM-1 on cytokine-stimulated endothelial cells. Examination of the actin cytoskeleton on IL-1beta-activated endothelial cells showed that both 4 and 24 h of incubation with simvastatin produced a complete disappearance of F-actin, being completely restored by MVA and partially by GGPP and FPP after 24 h of coincubation. We suggest that cytoskeleton disorganization in endothelial cells is important for inhibiting monocyte adhesion, altering the adhesion molecules function. Taken together, these results strongly support the beneficial anti-inflammatory properties of statins, contributing to the overall clinical effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / drug effects
  • Actins / physiology
  • Anticholesteremic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL2 / pharmacology
  • Cytoskeleton / drug effects
  • Endothelial Cells / drug effects*
  • Endothelial Cells / physiology
  • Humans
  • Interleukin-1beta / pharmacology
  • Mevalonic Acid / pharmacology
  • Monocytes / drug effects*
  • Monocytes / physiology
  • Polyisoprenyl Phosphates / pharmacology
  • Sesquiterpenes
  • Simvastatin / pharmacology*


  • Actins
  • Anticholesteremic Agents
  • CCL2 protein, human
  • Chemokine CCL2
  • Interleukin-1beta
  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • farnesyl pyrophosphate
  • Simvastatin
  • geranylgeranyl pyrophosphate
  • Mevalonic Acid