Highlighted paper selected by editor-in-chief: Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions
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- Ii Hiromi
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Hontani Naoya
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Toshida Issei
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Oka Mayuko
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Sato Takashi
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Akiba Satoshi
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
書誌事項
- タイトル別名
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- Group IVA Phospholipase A2-Associated Production of MMP-9 in Macrophages and Formation of Atherosclerotic Lesions
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Matrix metalloproteinase-9 (MMP-9) is involved in atherogenesis, and the production of MMP-9 in macrophages is considered to be mediated by the arachidonic acid cascade. The present study examined the possible involvement of group IVA phospholipase A2 (IVA-PLA2), a key enzyme in the arachidonic acid cascade, in the production of MMP-9 induced by oxidized low-density lipoprotein (oxLDL) in macrophages and high-fat diet-induced formation of atherosclerotic lesions using IVA-PLA2-deficient mice (C57BL/6 background). In wild-type mouse peritoneal macrophages, oxLDL induced an increase in MMP-9 in the culture medium. The oxLDL-promoted production of MMP-9 was markedly reduced in IVA-PLA2-deficient macrophages compared to wild-type macrophages. Feeding of wild-type mice with a high-fat diet caused the formation of early atherosclerotic lesions in the aortic root with increases in MMP-9 and macrophages in the lesions and with higher serum levels of total cholesterol. Such lesions were apparently less severe in IVA-PLA2-deficient mice fed a high-fat diet, despite higher total cholesterol levels. Under the conditions, a high-fat diet reduced the serum levels of high-density lipoprotein-cholesterol (HDL-C) in wild-type mice. However, IVA-PLA2-deficient mice fed a high-fat diet were protected against the decrease in HDL-C levels. The present results suggest that IVA-PLA2 is involved in the oxLDL-induced production of MMP-9 in macrophages and the high-fat diet-induced formation of early atherosclerotic lesions. The protection against the lesions in IVA-PLA2-deficient mice may be ascribable, in part, to the impaired production of MMP-9 and/or the maintained levels of HDL-C.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 31 (3), 363-368, 2008
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679602512128
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- NII論文ID
- 110006623057
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 9393069
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
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- 抄録ライセンスフラグ
- 使用不可