RRC ID |
39188
|
著者 |
Ramos MA, Kuzuya M, Esaki T, Miura S, Satake S, Asai T, Kanda S, Hayashi T, Iguchi A.
|
タイトル |
Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions.
|
ジャーナル |
Arterioscler Thromb Vasc Biol
|
Abstract |
The interaction between macrophages and oxidatively modified low density lipoprotein (Ox-LDL) appears to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the induction of numerous cytokines and growth factors. The current study demonstrated that Ox-LDL upregulated vascular endothelial growth factor (VEGF) mRNA expression in RAW 264 cells, a monocytic cell line, in a time- and concentration-dependent manner and that Ox-LDL stimulated VEGF protein secretion from the cells. Lysophosphatidylcholine, a component of Ox-LDL, also enhanced VEGF mRNA expression in RAW 264 cells and VEGF secretion from RAW 264 cells, with a maximal effect at a concentration of 10 micromol/L lysophosphatidylcholine. Immunohistochemical studies showed that human early atherosclerotic lesions exhibited intense VEGF immunoreactivity in subendothelial macrophage-rich regions of the thickened intima. In atherosclerotic plaques, VEGF staining was also observed in foam cell-rich regions adjacent to the lipid core or the neovascularized basal regions of plaque consisting predominantly of smooth muscle cells. High-power-field observation revealed that VEGF was localized in the extracellular space as well as at the macrophage cell surface. These observations suggest the possible involvement of Ox-LDL in the development of human atherosclerosis through VEGF induction in macrophages.
|
巻・号 |
18(7)
|
ページ |
1188-96
|
公開日 |
1998-7-1
|
DOI |
10.1161/01.atv.18.7.1188
|
PMID |
9672081
|
MeSH |
3T3 Cells
Animals
Arteriosclerosis / metabolism*
Blotting, Northern
Culture Media, Conditioned
Endothelial Growth Factors / analysis
Endothelial Growth Factors / biosynthesis*
Endothelial Growth Factors / genetics
Gene Expression Regulation / drug effects
Humans
Immunohistochemistry
Lipoproteins, LDL / pharmacology*
Lymphokines / analysis
Lymphokines / biosynthesis*
Lymphokines / genetics
Lysophosphatidylcholines / pharmacology
Macrophages / metabolism*
Mice
RNA, Messenger / metabolism
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
|
IF |
6.604
|
引用数 |
122
|
WOS 分野
|
HEMATOLOGY
PERIPHERAL VASCULAR DISEASE
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |