Orally administered eicosapentaenoic acid reduces and stabilizes atherosclerotic lesions in ApoE-deficient mice
Orally administered eicosapentaenoic acid reduces and stabilizes atherosclerotic lesions in ApoE-deficient mice
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DOI：
10.1016/j.atherosclerosis.2007.07.023
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发表时间：
2008-04-01
期刊：
影响因子：
5.3
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
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作者：
Matsumoto, Miwa;Sata, Masataka;Nagai, Ryozo
越来越多的证据表明，饮食中摄入n-3多不饱和脂肪酸（PUFAs）与降低心血管事件发生率有关。然而，n-3 PUFAs预防动脉粥样硬化的分子机制尚不完全清楚。在这里，我们研究了二十碳五烯酸（EPA），一种主要的n-3 PUFA，对apoe缺陷小鼠动脉粥样硬化发病机制的影响。5周龄apoe缺陷雄性小鼠分别饲喂添加5% (w/w) EPA （EPA组，n = 7）和不添加EPA（对照组，n = 5）的西式饲粮13周。肝脏匀浆脂肪酸组成分析显示，EPA组n-3 PUFA含量显著增加（n-3/n-6比值：0.20 +/- 0.01 vs. 2.5 +/- 0.2, p < 0.01）。主动脉的En face Sudan IV染色和主动脉窦的油红o染色显示，EPA显著抑制动脉粥样硬化病变的发展。我们还观察到EPA在ldl受体缺陷小鼠中的抗动脉粥样硬化作用。EPA组病变中胶原蛋白（19.6 +/- 2.4% vs. 32.9 +/- 3.9%, p < 0.05）、平滑肌细胞（1.3 +/- 0.2% vs. 3.6 +/- 0.8%, p < 0.05）、巨噬细胞（32.7 +/- 4.1% vs. 14.7 +/- 2.0%, p < 0.05）含量较高。EPA预处理可减弱tnf - α诱导的巨噬细胞样细胞中VCAM-1、ICAM-1和MCP-1在huvec中的上调，以及MMP-2和MMP-9的表达。当过氧化物酶体增殖物激活受体α (PPAR α)的表达被抑制时，EPA的抗炎作用被取消。EPA可能通过其抗炎作用潜在地减少和稳定动脉粥样硬化病变。2007爱思唯尔爱尔兰有限公司版权所有。
Accumulating evidence demonstrates that dietary intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced incidence of cardiovascular events. However, the molecular mechanisms by which n-3 PUFAs prevent atherosclerosis are not fully understood. Here, we examined the effect of eicosapentaenoic acid (EPA), a major n-3 PUFA, on the pathogenesis of atherosclerosis in ApoE-deficient mice. Five-week-old ApoE-deficient male mice were fed on western-type diet supplemented with 5% (w/w) EPA (EPA group, n = 7) or not (control group, it = 5) for 13 weeks. An analysis of the fatty acid composition of liver homogenates revealed a marked increase of the n-3 PUFA content in the EPA group (n-3/n-6 ratio: 0.20 +/- 0.01 vs. 2.5 +/- 0.2, p < 0.01). En face Sudan IV staining of the aorta and oil red O-staining of the aortic sinus revealed that EPA significantly suppressed the development of atherosclerotic lesions. We also observed anti-atherosclerotic effects of EPA in LDL-receptor-deficient mice. The lesions of the EPA group contained more collagen (19.6 +/- 2.4% vs. 32.9 +/- 3.9%, p < 0.05) and smooth muscle cells (1.3 +/- 0.2% vs. 3.6 +/- 0.8%, p < 0.05) and less macrophages (32.7 +/- 4.1% vs. 14.7 +/- 2.0%, p < 0.05). Pretreatment with EPA attenuated the up-regulation of VCAM-1, ICAM-1 and MCP-1 in HUVECs as well as the expression of MMP-2 and MMP-9 in macrophage-like cells induced by TNF-alpha. The anti-inflammatory effects of EPA were abrogated when the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) was suppressed. EPA may potentially reduce and stabilize atherosclerotic lesions through its anti-inflammatory effects. (C) 2007 Elsevier Ireland Ltd. All rights reserved.