Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2

TT Tuomisto, H Lumivuori, E Kansanen… - Cardiovascular …, 2008 - academic.oup.com
TT Tuomisto, H Lumivuori, E Kansanen, SK Häkkinen, MP Turunen, JV Van Thienen…
Cardiovascular research, 2008academic.oup.com
Aims Statins have beneficial vascular effects beyond their cholesterol-lowering action. Since
macrophages play a central role in atherogenesis, we characterized the effects of
simvastatin on gene expression profile of human peripheral blood monocyte (HPBM)-
macrophages. Methods and results Gene expression profile was studied using Affymetrix
gene chip analysis. Lentiviral gene transfer of Kruppel-like factor 2 (KLF-2) was used to
further study its role in macrophages. Simvastatin treatment lead to downregulation of many …
Aims
Statins have beneficial vascular effects beyond their cholesterol-lowering action. Since macrophages play a central role in atherogenesis, we characterized the effects of simvastatin on gene expression profile of human peripheral blood monocyte (HPBM)-macrophages.
Methods and results
Gene expression profile was studied using Affymetrix gene chip analysis. Lentiviral gene transfer of Kruppel-like factor 2 (KLF-2) was used to further study its role in macrophages. Simvastatin treatment lead to downregulation of many pro-inflammatory genes including several chemokines [e.g. monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory proteins-1α and β, interleukin-2 receptor-β], members of the tumour necrosis factor family (e.g. lymphotoxin β), vascular cell adhesion molecule-1, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for inflammation: NF-κB relA/p65 subunit and ets-1 were downregulated, and an atheroprotective transcription factor KLF-2 was upregulated. The effects of simvastatin on MCP-1 and TF could be mimicked by KLF-2 overexpression using lentiviral gene transfer.
Conclusion
Simvastatin has a strong anti-inflammatory effect on HPBM cells including upregulation of the atheroprotective factor KLF-2. This may partly explain the beneficial effects of statins on cardiovascular diseases.
Oxford University Press