PMID- 26556845
OWN - NLM
STAT- MEDLINE
DCOM- 20161101
LR  - 20171116
IS  - 1689-1392 (Electronic)
IS  - 1425-8153 (Linking)
VI  - 20
IP  - 5
DP  - 2015 Dec
TI  - Cerivastatin represses atherogenic gene expression through the induction of KLF2 
      via isoprenoid metabolic pathways.
PG  - 825-39
LID - 10.1515/cmble-2015-0049 [doi]
AB  - Earlier clinical studies have reported that cerivastatin has an 
      anti-atherosclerotic effect that is unique among the statins. In our study, human 
      THP-1 macrophage cells were used to study the effects of various statins on the 
      expressions of the atherosclerotic genes and Kruppel-like factor 2 (KLF2). 
      Cerivastatin significantly inhibited the two atherosclerotic genes, monocyte 
      chemoattractant protein-1 (MCP-1) and C-C chemokine receptor type 2 (CCR2) at 
      both the mRNA and protein levels, while the other statins did not. Accordingly, 
      cerivastatin was also the most potent inducer of KLF2 transcription in the 
      macrophages. An siRNA-induced reduction in KLF2 expression blocked the inhibition 
      of MCP-1 and CCR2 by cerivastatin. When the cells were further treated with 
      mevalonate, farnesylpyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP), 
      the effects of cerivastatin on KLF2, MCP-1 and CCR2 were obviously reversed. 
      Thus, the results showed that cerivastatin was a potent inhibitor of the 
      inflammation genes MCP-1 and CCR2 through the induction of KLF2. The regulation 
      of MCP-1, CCR2 and KLF2 by cerivastatin was isoprenoid pathway dependent. Our 
      studies suggest that the effect of cerivastatin on atherosclerotic genes and KLF2 
      expression may contribute to the cardioprotection observed in reported clinical 
      studies.
FAU - Zhao, Jiyuan
AU  - Zhao J
FAU - Natarajan, Selvamuthu K
AU  - Natarajan SK
FAU - Chronos, Nicolas
AU  - Chronos N
FAU - Singh, Jai Pal
AU  - Singh JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Mol Biol Lett
JT  - Cellular & molecular biology letters
JID - 9607427
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (KLF2 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Polyisoprenyl Phosphates)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Terpenes)
RN  - 79W6B01D07 (farnesyl pyrophosphate)
RN  - AM91H2KS67 (cerivastatin)
RN  - N21T0D88LX (geranylgeranyl pyrophosphate)
RN  - S5UOB36OCZ (Mevalonic Acid)
SB  - IM
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/genetics/metabolism
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Kruppel-Like Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - Metabolic Networks and Pathways/drug effects
MH  - Mevalonic Acid/pharmacology
MH  - Polyisoprenyl Phosphates/pharmacology
MH  - Pyridines/*pharmacology
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, CCR2/genetics/metabolism
MH  - Sesquiterpenes/pharmacology
MH  - Terpenes/*metabolism
EDAT- 2015/11/12 06:00
MHDA- 2016/11/02 06:00
CRDT- 2015/11/12 06:00
PHST- 2015/07/02 00:00 [received]
PHST- 2015/10/22 00:00 [accepted]
PHST- 2015/11/12 06:00 [entrez]
PHST- 2015/11/12 06:00 [pubmed]
PHST- 2016/11/02 06:00 [medline]
AID - /j/cmble.ahead-of-print/cmble-2015-0049/cmble-2015-0049.xml [pii]
AID - 10.1515/cmble-2015-0049 [doi]
PST - ppublish
SO  - Cell Mol Biol Lett. 2015 Dec;20(5):825-39. doi: 10.1515/cmble-2015-0049.