PMID- 20619710
OWN - NLM
STAT- MEDLINE
DCOM- 20110124
LR  - 20240320
IS  - 1096-7206 (Electronic)
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 101
IP  - 1
DP  - 2010 Sep
TI  - Mitogen-activated protein kinase phosphatase-1 deficiency decreases 
      atherosclerosis in apolipoprotein E null mice by reducing monocyte 
      chemoattractant protein-1 levels.
PG  - 66-75
LID - 10.1016/j.ymgme.2010.05.009 [doi]
AB  - RATIONALE: We previously reported that mitogen-activated protein kinase 
      phosphatase-1 (MKP-1) expression is necessary for oxidized phospholipids to 
      induce monocyte chemoattractant protein-1 (MCP-1) secretion by human aortic 
      endothelial cells. We also reported that inhibition of tyrosine phosphatases 
      including MKP-1 ameliorated atherosclerotic lesions in mouse models of 
      atherosclerosis. OBJECTIVE: This study was conducted to further investigate the 
      specific role of MKP-1 in atherogenesis. METHODS AND RESULTS: We generated 
      MKP-1(-/-)/apoE(-/-) double-knockout mice. At 24weeks of age, the size, 
      macrophage and dendritic cell content of atherosclerotic lesions of the aortic 
      root were significantly lower ( approximately -41% for lesions and macrophages, 
      and approximately -78% for dendritic cells) in MKP-1(-/-)/apoE(-/-) mice when 
      compared with apoE(-/-) mice. Total cholesterol (-18.4%, p=0.045) and very 
      low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) cholesterol (-20.0%, 
      p=0.052) levels were decreased in MKP-1(-/-)/apoE(-/-) mice. Serum from 
      MKP-1(-/-)/apoE(-/-) mice contained significantly lower levels of MCP-1 and 
      possessed significantly reduced capability to induce monocyte migration in vitro. 
      Moreover, peritoneal macrophages isolated from MKP-1(-/-)/apoE(-/-) mice produced 
      significantly lower levels of MCP-1 when compared to peritoneal macrophages from 
      apoE(-/-) mice. Furthermore, MKP-1(-/-)/apoE(-/-) mice had significantly reduced 
      serum hydroxyeicosatetraenoic acids (HETEs) levels, which have been reported to 
      induce MCP-1 levels. CONCLUSIONS: Our results demonstrate that MKP-1 deficiency 
      significantly decreases atherosclerotic lesion development in mice, in part, by 
      affecting MCP-1 levels in the circulation and MCP-1 production by macrophages. 
      MKP-1 may serve as a potential therapeutic target for the treatment of 
      atherosclerotic disease.
FAU - Imaizumi, Satoshi
AU  - Imaizumi S
AD  - Department of Medicine, David Geffen School of Medicine, University of California 
      Los Angeles, CA 90095-1679, USA.
FAU - Grijalva, Victor
AU  - Grijalva V
FAU - Priceman, Saul
AU  - Priceman S
FAU - Wu, Lily
AU  - Wu L
FAU - Su, Feng
AU  - Su F
FAU - Farias-Eisner, Robin
AU  - Farias-Eisner R
FAU - Hama, Susan
AU  - Hama S
FAU - Navab, Mohamad
AU  - Navab M
FAU - Fogelman, Alan M
AU  - Fogelman AM
FAU - Reddy, Srinivasa T
AU  - Reddy ST
LA  - eng
GR  - HL 082823/HL/NHLBI NIH HHS/United States
GR  - P01 HL030568/HL/NHLBI NIH HHS/United States
GR  - P01 HL030568-27/HL/NHLBI NIH HHS/United States
GR  - HL-30568/HL/NHLBI NIH HHS/United States
GR  - R01 HL082823/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100609
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Atherosclerosis/*enzymology/genetics/metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Dual Specificity Phosphatase 1/deficiency/*genetics/metabolism
MH  - Hydroxyeicosatetraenoic Acids/blood
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
PMC - PMC3037189
MID - NIHMS213929
EDAT- 2010/07/14 06:00
MHDA- 2011/01/25 06:00
PMCR- 2011/09/01
CRDT- 2010/07/13 06:00
PHST- 2010/05/20 00:00 [received]
PHST- 2010/05/20 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2011/01/25 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - S1096-7192(10)00212-X [pii]
AID - 10.1016/j.ymgme.2010.05.009 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2010 Sep;101(1):66-75. doi: 10.1016/j.ymgme.2010.05.009. Epub 
      2010 Jun 9.