RRC ID 41586
Author Yamashita T, Kawashima S, Ozaki M, Namiki M, Inoue N, Hirata K, Yokoyama M.
Title Propagermanium reduces atherosclerosis in apolipoprotein E knockout mice via inhibition of macrophage infiltration.
Journal 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.
Volume 22(6)
Pages 969-74
Published 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* Thioglycolates / pharmacology
IF 6.086
Times Cited 19
Human and Animal Cells