PMID- 16040051
OWN - NLM
STAT- MEDLINE
DCOM- 20051025
LR  - 20141202
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 39
IP  - 3
DP  - 2005 Sep
TI  - Cyclooxygenase-2 promotes early atherosclerotic lesion formation in 
      ApoE-deficient and C57BL/6 mice.
PG  - 443-52
AB  - Cyclooxygenase (COX) 2 is expressed in atherosclerotic lesions. We have 
      previously reported that selective inhibition of COX-2 reduces early 
      atherosclerosis in LDLR deficient mice. To examine the role of COX-2 in 
      atherosclerosis in other mouse models, we studied the effects of selective COX-2 
      inhibition (by rofecoxib and NS-398) and nonselective COX inhibition (by 
      indomethacin) on early atherosclerotic lesion formation in apolipoprotein 
      E-deficient (apoE(-/-)) mice. Selective COX-2 and nonselective COX inhibition 
      reduced atherosclerosis in female apoE(-/-) mice by 35-38% and 38-51% in the 
      proximal and en face aortas, respectively. Next we investigated the role of 
      macrophage COX-2 by transplanting COX-2(-/-) fetal liver cells into C57BL/6 mice 
      and challenging the mice with an atherogenic diet. Genetic deletion of COX-2 from 
      hematopoietic cells reduced atherosclerosis by 51%. In addition, LPS activated 
      COX-2(-/-) macrophages had decreased expression of monocyte chemoattractant 
      protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFalpha). The results 
      demonstrate that selective inhibition of COX-2 and elimination of COX-2 from 
      macrophages significantly reduces early atherosclerotic lesion formation in 
      apoE-deficient and C57BL/6 mice. These results are compatible with COX-2 
      expression by macrophages having a proatherogenic role, and support the potential 
      of anti-inflammatory therapeutic approaches for atherosclerosis.
FAU - Burleigh, Michael E
AU  - Burleigh ME
AD  - Department of Pharmacology, 383 Preston Research Building, Vanderbilt University 
      Medical Center, Nashville, TN 37232-6300, USA.
FAU - Babaev, Vladimir R
AU  - Babaev VR
FAU - Yancey, Patricia G
AU  - Yancey PG
FAU - Major, Amy S
AU  - Major AS
FAU - McCaleb, Jennifer L
AU  - McCaleb JL
FAU - Oates, John A
AU  - Oates JA
FAU - Morrow, Jason D
AU  - Morrow JD
FAU - Fazio, Sergio
AU  - Fazio S
FAU - Linton, Macrae F
AU  - Linton MF
LA  - eng
GR  - DK59637/DK/NIDDK NIH HHS/United States
GR  - HL53989/HL/NHLBI NIH HHS/United States
GR  - HL57986/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Lactones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0QTW8Z7MCR (rofecoxib)
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/pathology
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Arteriosclerosis/enzymology/*etiology/genetics/*pathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Female
MH  - Immunohistochemistry
MH  - Indomethacin/pharmacology
MH  - Lactones/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Liver Transplantation
MH  - Macrophages/enzymology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitrobenzenes/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Sulfonamides/pharmacology
MH  - Sulfones/pharmacology
MH  - Transplantation, Heterologous
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2005/07/26 09:00
MHDA- 2005/10/26 09:00
CRDT- 2005/07/26 09:00
PHST- 2004/12/14 00:00 [received]
PHST- 2005/04/08 00:00 [revised]
PHST- 2005/06/13 00:00 [accepted]
PHST- 2005/07/26 09:00 [pubmed]
PHST- 2005/10/26 09:00 [medline]
PHST- 2005/07/26 09:00 [entrez]
AID - S0022-2828(05)00195-1 [pii]
AID - 10.1016/j.yjmcc.2005.06.011 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2005 Sep;39(3):443-52. doi: 10.1016/j.yjmcc.2005.06.011.