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

Abstract:

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-1alpha and beta, interleukin-2 receptor-beta], members of the tumour necrosis factor family (e.g. lymphotoxin beta), vascular cell adhesion molecule-1, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for inflammation: NF-kappaB 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Tuomisto TT,Lumivuori H,Kansanen E,Häkkinen SK,Turunen MP,van Thienen JV,Horrevoets AJ,Levonen AL,Ylä-Herttuala S

doi

10.1093/cvr/cvn007

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

175-84

issue

1

eissn

0008-6363

issn

1755-3245

pii

cvn007

journal_volume

78

pub_type

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