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)