| RRC ID |
41586
|
| 著者 |
Yamashita T, Kawashima S, Ozaki M, Namiki M, Inoue N, Hirata K, Yokoyama M.
|
| タイトル |
Propagermanium reduces atherosclerosis in apolipoprotein E knockout mice via inhibition of macrophage infiltration.
|
| ジャーナル |
Arterioscler Thromb Vasc Biol
|
| Abstract |
Monocyte chemoattractant protein-1 (MCP-1), which binds to C-C chemokine receptor 2, has been implicated as the primary source of monocyte chemoattractant function in the early stages of atherosclerosis. Recently, propagermanium, a drug used clinically for the treatment of chronic hepatitis in Japan, has been shown to inhibit C-C chemokine receptor 2 function and suppress monocyte/macrophage infiltration in vitro and in vivo. Given the importance of monocyte infiltration in atherogenesis, the inhibition of it by propagermanium might prevent atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were fed an atherogenic high cholesterol diet with or without 0.005% propagermanium for 8 or 12 weeks. Although the plasma lipid levels were unchanged by the drug treatment, atherosclerotic lesion area in the aortic root was reduced by 50% in the drug-treated apoE-KO mice compared with the nontreated apoE-KO mice after 8 weeks of cholesterol feeding (0.62+/-0.12 versus 1.27+/-0.07 mm2, respectively; P<0.01). Moreover, the accumulation of macrophages in the lesions was markedly reduced in the drug-treated group (macrophage positive area, 0.23+/-0.06 mm2 [drug-treated group] versus 0.67+/-0.07 mm2 [control group]; P<0.01). After 12 weeks of cholesterol feeding, atherosclerotic lesion formation in the aortic root and in the descending thoracic aorta was significantly reduced in the drug-treated group. Inhibition of macrophage infiltration by propagermanium prevented the formation of atherosclerotic lesions in apoE-KO mice. This drug may serve as a therapeutic tool for the treatment of atherosclerosis.
|
| 巻・号 |
22(6)
|
| ページ |
969-74
|
| 公開日 |
2002-6-1
|
| DOI |
10.1161/01.atv.0000019051.88366.9c
|
| PMID |
12067906
|
| MeSH |
Abdomen
Animals
Apolipoproteins E / deficiency*
Apolipoproteins E / genetics*
Apolipoproteins E / physiology
Arteriosclerosis / genetics
Arteriosclerosis / pathology
Arteriosclerosis / prevention & control*
Cell Adhesion / drug effects
Cell Adhesion / physiology
Cell Line
Cell Migration Inhibition*
Cells, Cultured
Chemokine CCL2 / antagonists & inhibitors
Chemokine CCL2 / physiology
Cholesterol, Dietary / administration & dosage
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects
Endothelium, Vascular / physiology
Female
Germanium / therapeutic use*
Lipids / blood
Macrophage Activation / drug effects
Macrophages / drug effects*
Macrophages / pathology*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes / drug effects
Monocytes / physiology
Organometallic Compounds / therapeutic use*
Propionates
Thioglycolates / pharmacology
|
| IF |
6.604
|
| 引用数 |
21
|
|
WOS 分野
|
HEMATOLOGY
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| ヒト・動物細胞 |
|
