PMID- 18192240
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20231002
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 78
IP  - 1
DP  - 2008 Apr 1
TI  - Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an 
      atheroprotective transcription factor, Kruppel-like factor 2.
PG  - 175-84
LID - 10.1093/cvr/cvn007 [doi]
AB  - 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.
FAU - Tuomisto, Tiina T
AU  - Tuomisto TT
AD  - Department of Biotechnology and Molecular Medicine, A I Virtanen Institute, 
      University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
FAU - Lumivuori, Henri
AU  - Lumivuori H
FAU - Kansanen, Emilia
AU  - Kansanen E
FAU - Hakkinen, Sanna-Kaisa
AU  - Hakkinen SK
FAU - Turunen, Mikko P
AU  - Turunen MP
FAU - van Thienen, Johannes V
AU  - van Thienen JV
FAU - Horrevoets, Anton J
AU  - Horrevoets AJ
FAU - Levonen, Anna-Liisa
AU  - Levonen AL
FAU - Yla-Herttuala, Seppo
AU  - Yla-Herttuala S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080110
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (KLF2 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (RELA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factors)
RN  - 9035-58-9 (Thromboplastin)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/genetics/*metabolism
MH  - Gene Expression Profiling/methods
MH  - Gene Transfer Techniques
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Kruppel-Like Transcription Factors/genetics/*metabolism
MH  - Macrophages/*drug effects/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Protein Prenylation
MH  - Proto-Oncogene Proteins c-ets/metabolism
MH  - RNA, Messenger/metabolism
MH  - Simvastatin/*pharmacology
MH  - Thromboplastin/metabolism
MH  - Time Factors
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factors/metabolism
MH  - Up-Regulation
EDAT- 2008/01/15 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/01/15 09:00
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - cvn007 [pii]
AID - 10.1093/cvr/cvn007 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2008 Apr 1;78(1):175-84. doi: 10.1093/cvr/cvn007. Epub 2008 Jan 
      10.