PMID- 15823270
OWN - NLM
STAT- MEDLINE
DCOM- 20050728
LR  - 20220310
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 180
IP  - 1
DP  - 2005 May
TI  - Disruption of tumor necrosis factor-alpha gene diminishes the development of 
      atherosclerosis in ApoE-deficient mice.
PG  - 11-7
AB  - Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) have 
      been implicated in atherogenesis. However, the precise role of TNF-alpha in 
      atherogenesis is still unclear. To examine the effect of TNF-alpha on 
      atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) 
      and TNF-alpha (apoE-/-/TNF-alpha-/-) and compared them with apoE-/- mice. 
      Although serum total cholesterol levels were markedly elevated in both 
      apoE-/-/TNF-alpha-/- and apoE-/- mice compared to wild-type mice, no differences 
      were observed between apoE-/-/TNF-alpha-/- and apoE-/- mice. The atherosclerotic 
      plaque area in the aortic luminal surface of apoE-/-/TNF-alpha-/- mice (n=8, 
      3.1+/-0.4%) was significantly smaller than that of apoE-/- mice (n=7, 4.7+/-0.4%, 
      p<0.001) despite the lack of difference in serum cholesterol levels. The 
      atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-alpha-/- mice 
      (n=10, 5.1+/-0.3 x 10(5)microm(2)) was also significantly smaller than that of 
      apoE-/- mice (n=11, 7.0+/-0.3 x 10(5)microm(2), p<0.0001). RT-PCR analysis 
      indicated that the expression levels of intercellular adhesion molecule-1 
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant 
      protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF-alpha-/- 
      mice. Macrophages from apoE(-/-) mice showed higher uptake level of oxidized LDL 
      and increased expression level of scavenger receptor class A (SRA) compared to 
      those from apoE-/-/TNF-alpha-/- mice. These results indicate that TNF-alpha plays 
      an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 
      in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in 
      macrophages.
FAU - Ohta, Hirotoshi
AU  - Ohta H
AD  - Department of Clinical Laboratory Medicine, Gifu University School of Medicine 
      1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
FAU - Wada, Hisayasu
AU  - Wada H
FAU - Niwa, Tamikazu
AU  - Niwa T
FAU - Kirii, Hirokazu
AU  - Kirii H
FAU - Iwamoto, Naoki
AU  - Iwamoto N
FAU - Fujii, Hidehiko
AU  - Fujii H
FAU - Saito, Kuniaki
AU  - Saito K
FAU - Sekikawa, Kenji
AU  - Sekikawa K
FAU - Seishima, Mitsuru
AU  - Seishima M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050120
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Aorta/pathology/physiopathology
MH  - Apolipoproteins E/*genetics
MH  - Arteriosclerosis/*genetics/pathology/*physiopathology
MH  - Chemokine CCL2/genetics
MH  - Cholesterol, HDL/blood
MH  - Female
MH  - Gene Expression
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Triglycerides/blood
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - Vascular Cell Adhesion Molecule-1/genetics
EDAT- 2005/04/13 09:00
MHDA- 2005/07/29 09:00
CRDT- 2005/04/13 09:00
PHST- 2004/02/16 00:00 [received]
PHST- 2004/11/03 00:00 [revised]
PHST- 2004/11/19 00:00 [accepted]
PHST- 2005/04/13 09:00 [pubmed]
PHST- 2005/07/29 09:00 [medline]
PHST- 2005/04/13 09:00 [entrez]
AID - S0021-9150(04)00624-0 [pii]
AID - 10.1016/j.atherosclerosis.2004.11.016 [doi]
PST - ppublish
SO  - Atherosclerosis. 2005 May;180(1):11-7. doi: 
      10.1016/j.atherosclerosis.2004.11.016. Epub 2005 Jan 20.