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欧米伽3多不饱和脂肪酸通过抑制巨噬细胞介导的炎症反应来抑制主动脉瘤的发展。

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation.

作者信息

Yoshihara Takuma, Shimada Kazunori, Fukao Kosuke, Sai Eiryu, Sato-Okabayashi Yayoi, Matsumori Rie, Shiozawa Tomoyuki, Alshahi Hamad, Miyazaki Tetsuro, Tada Norihiro, Daida Hiroyuki

机构信息

Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine.

出版信息

Circ J. 2015;79(7):1470-8. doi: 10.1253/circj.CJ-14-0471. Epub 2015 Apr 30.

Abstract

BACKGROUND

Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration.

CONCLUSIONS

Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

摘要

背景

饮食中摄入ω3多不饱和脂肪酸(ω3-PUFAs)可减缓动脉粥样硬化进展并预防未来心血管事件。巨噬细胞是主动脉瘤发病机制中的关键因素。ω3-PUFAs对腹主动脉瘤(AAA)形成及巨噬细胞介导的炎症的影响尚不清楚。

方法与结果

通过给载脂蛋白E缺陷小鼠输注血管紧张素II建立AAA模型。给小鼠补充二十碳五烯酸(EPA)或二十二碳六烯酸(DHA)。分析AAA病变的发展及主动脉中巨噬细胞的浸润情况。采用定量聚合酶链反应检测主动脉组织和腹膜巨噬细胞中炎症标志物的基因表达。给予EPA和DHA后,AAA形成及巨噬细胞浸润均受到显著抑制。给予EPA和DHA后,主动脉中肿瘤坏死因子-α、单核细胞趋化蛋白-1、转化生长因子-β、基质金属蛋白酶(MMP)-2、MMP-9和血管细胞黏附分子-1的表达显著降低。促炎巨噬细胞标志物精氨酸酶2的表达显著降低,而抗炎巨噬细胞标志物Ym1的表达在给予EPA和DHA后显著升高。给予EPA和DHA后,腹膜巨噬细胞也观察到相同趋势。

结论

饮食中摄入EPA和DHA可通过抑制主动脉及巨噬细胞介导的炎症来预防AAA的发展。

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