RRC ID 43598
著者 Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata H, Kawazu S, Higashi Y, Kurihara H, Asano T.
タイトル Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development.
ジャーナル Arterioscler Thromb Vasc Biol
Abstract OBJECTIVE:Hyperuricemia is common in patients with metabolic syndrome. We investigated the role of xanthine oxidoreductase (XOR) in atherosclerosis development, and the effects of the XOR inhibitor allopurinol on this process.
METHODS AND RESULTS:Oral administration of allopurinol to ApoE knockout mice markedly ameliorated lipid accumulation and calcification in the aorta and aortic root. In addition, allopurinol treatment or siRNA-mediated gene knockdown of XOR suppressed transformation of J774.1 murine macrophage cells, treated with acetylated LDL or very low density lipoprotein (VLDL) into foam cells. This inhibitory effect of allopurinol was also observed in primary cultured human macrophages. In contrast, overexpression of XOR promoted transformation of J774.1 cells into foam cells. Interestingly, SR-A1, SR-B1, SR-B II, and VLDL receptors in J774.1 cells were reduced by XOR knockdown, and increased by XOR overexpression. Conversely, expressions of ABCA1 and ABCG1 were increased by XOR knockdown and suppressed by XOR overexpression. Finally, productions of inflammatory cytokines accompanied by foam cell formation were also reduced by allopurinol administration.
CONCLUSIONS:These results strongly suggest XOR activity and/or its expression level to contribute to macrophage foam cell formation. Thus, XOR inhibitors may be useful for preventing atherosclerosis.
巻・号 32(2)
ページ 291-8
公開日 2012-2-1
DOI 10.1161/ATVBAHA.111.234559
PII ATVBAHA.111.234559
PMID 22095983
MeSH ATP Binding Cassette Transporter 1 ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters / metabolism Allopurinol / pharmacology Animals Apolipoproteins E / deficiency Apolipoproteins E / genetics Atherosclerosis / metabolism* Atherosclerosis / physiopathology* Cell Differentiation / physiology* Cells, Cultured Cytokines / metabolism Disease Models, Animal Enzyme Inhibitors / pharmacology Foam Cells / drug effects Foam Cells / metabolism Foam Cells / pathology* Humans Lipid Metabolism / drug effects Lipoproteins / metabolism Macrophages / drug effects Macrophages / metabolism Macrophages / pathology* Mice Mice, Knockout Xanthine Dehydrogenase / antagonists & inhibitors Xanthine Dehydrogenase / drug effects Xanthine Dehydrogenase / physiology*
IF 6.604
引用数 62
WOS 分野 PERIPHERAL VASCULAR DISEASE HEMATOLOGY
リソース情報
ヒト・動物細胞 J774.1