Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice
Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice
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DOI：
10.1161/01.cir.0000143628.37680.f6
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发表时间：
2004-10-05
期刊：
影响因子：
37.8
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Huo, YQ;Zhao, L;Ley, K
缺乏白细胞型12/15-脂氧合酶（12/15-LO）的小鼠在几种模型中显示动脉粥样硬化减少。12/15-LO在多种细胞中表达，包括血管细胞、脂肪细胞、巨噬细胞和心肌细胞。本研究的目的是确定12/15-LO的细胞来源对动脉粥样硬化是重要的。方法和结果-将来自12/15-LO-/-/apoE（-/-）小鼠的骨髓移植到apoE（-/-）小鼠中，反之亦然。骨髓细胞中缺乏12/15-LO可保护apoE（-/-）小鼠免于动脉粥样硬化，其程度与完全缺乏12/15-LO相同，尽管血浆8，12-iso-iPF（2 α）-IV（脂质过氧化的一种测量）仍然升高。12/15-LO-/-/apoE（-/-）小鼠在用来自apoE（-/-）小鼠的骨髓替换它们的骨髓细胞后恢复了apoE（-/-）小鼠典型的动脉粥样硬化病变的严重性。从野生型而非12/15-LO-/-小鼠获得的腹膜巨噬细胞在天然LDL存在下引起内皮活化。缺乏12/15-LO降低了巨噬细胞形成泡沫细胞的能力，当暴露于LDL. Conclusions，我们得出结论，巨噬细胞12/15-LO起着主导作用，在动脉粥样硬化的发展，促进内皮炎症和泡沫细胞的形成。
Background-Mice lacking leukocyte type 12/15-lipoxygenase (12/15-LO) show reduced atherosclerosis in several models. 12/15-LO is expressed in a variety of cells, including vascular cells, adipocytes, macrophages, and cardiomyocytes. The purpose of this study was to determine which cellular source of 12/15-LO is important for atherosclerosis.Methods and Results-Bone marrow from 12/15-LO-/-/apoE(-/-) mice was transplanted into apoE(-/-) mice and vice versa. Deficiency of 12/15-LO in bone marrow cells protected apoE(-/-) mice fed a Western diet from atherosclerosis to the same extent as complete absence of 12/15-LO, although plasma 8,12-iso-iPF(2alpha)-IV, a measure of lipid peroxidation, remained elevated. 12/15-LO-/-/apoE(-/-) mice regained the severity of atherosclerotic lesion typical of apoE(-/-) mice after replacement of their bone marrow cells with bone marrow from apoE(-/-) mice. Peritoneal macrophages obtained from wild-type but not 12/15-LO-/- mice caused endothelial activation in the presence of native LDL. Absence of 12/15-LO decreased the ability of macrophages to form foam cells when exposed to LDL.Conclusions-We conclude that macrophage 12/15-LO plays a dominant role in the development of atherosclerosis by promoting endothelial inflammation and foam cell formation.