The ω-3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling.
The ω-3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling.
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DOI：
10.1371/journal.pone.0096286
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Manabe I
中科院分区：
文献类型：
--
作者：
Wang JH;Eguchi K;Matsumoto S;Fujiu K;Komuro I;Nagai R;Manabe I
腹主动脉瘤(AAA)是一种常见的血管疾病，可逐渐扩大和破裂，病死率高。炎症和主动的主动脉壁重构被认为在其发病机制中起关键作用。同时，ω-3多不饱和脂肪酸，如二十碳五烯酸，已知可减少心血管事件，但其在腹主动脉瘤管理中的作用尚不清楚。在这里，我们表明EPA可以减弱CaCl2诱导的小鼠AAA的形成。饲喂EPA饲料的BALB/c小鼠的主动脉炎症较轻，直径明显小于饲喂对照饲料的小鼠，并且相对保存了主动脉弹性膜。有趣的是，CT成像也显示EPA治疗后动脉钙化明显减少。从机制上讲，EPA治疗后，主动脉中MMP2、MMP9和TNFSF11水平降低。与这一发现一致的是，经EPA处理的RAW264.7巨噬细胞在肿瘤坏死因子-α模拟后显示MMP9水平降低。这些结果表明，EPA通过抑制AAA发病机制中的关键重塑通路，在抑制AAA的形成方面发挥了新的作用，并提高了在临床环境下使用EPA预防AAA的可能性。
Abdominal aortic aneurysm (AAA) is a prevalent vascular disease that can progressively enlarge and rupture with a high rate of mortality. Inflammation and active remodeling of the aortic wall have been suggested to be critical in its pathogenesis. Meanwhile, ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are known to reduce cardiovascular events, but its role in AAA management remains unclear. Here, we show that EPA can attenuate murine CaCl2-induced AAA formation. Aortas from BALB/c mice fed an EPA-diet appeared less inflamed, were significantly smaller in diameter compared to those from control-diet-fed mice, and had relative preservation of aortic elastic lamina. Interestingly, CT imaging also revealed markedly reduced calcification of the aortas after EPA treatment. Mechanistically, MMP2, MMP9, and TNFSF11 levels in the aortas were reduced after EPA treatment. Consistent with this finding, RAW264.7 macrophages treated with EPA showed attenuated Mmp9 levels after TNF-α simulation. These results demonstrate a novel role of EPA in attenuating AAA formation via the suppression of critical remodeling pathways in the pathogenesis of AAAs, and raise the possibility of using EPA for AAA prevention in the clinical setting.
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影响因子：
10.8
作者：
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通讯作者：
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影响因子：
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Longo, GM;Xiong, WF;Baxter, BT
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作者：
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DOI：
10.1161/atvbaha.106.136853
发表时间：
2007-09-01
影响因子：
8.7
作者：
Itoh, Michiko;Suganami, Takayoshi;Ogawa, Yoshihiro
通讯作者：
Ogawa, Yoshihiro