From the Department of Cellular and Molecular Anatomy (T. Sato, M.H., F.Y., T.K.I., T. Kondo, T. Sakurai, T. Kahyo, K.I., S.S., M.S.), Hamamatsu University School of Medicine, Shizuoka, Japan.
International Mass Imaging Center (T. Sato, M.H., F.Y., T.K.I., T. Kondo, T. Sakurai, T. Kahyo, K.I., S.S., M.S.), Hamamatsu University School of Medicine, Shizuoka, Japan.
Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1802-1816. doi: 10.1161/ATVBAHA.119.313093. Epub 2019 Aug 1.
n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on atherosclerosis. Although specific salutary actions have been reported, the detailed distribution of n-3 polyunsaturated fatty acids in plaque and their relevance in disease progression are unclear. Our aim was to assess the pharmacodynamics of EPA and DHA and their metabolites in atherosclerotic plaques. Approach and Results: Apolipoprotein E-deficient (Apoe) mice were fed a Western diet supplemented with EPA (1%, w/w) or DHA (1%, w/w) for 3 weeks. Imaging mass spectrometry analyses were performed in the aortic root and arch of the Apoe mice to evaluate the distribution of EPA, DHA, their metabolites and the lipids containing EPA or DHA in the plaques. Liquid chromatography-mass spectrometry and histological analysis were also performed. The intima-media thickness of atherosclerotic plaque decreased in plaques containing free EPA and EPAs attached with several lipids. EPA was distributed more densely in the thin-cap plaques than in the thick-cap plaques, while DHA was more evenly distributed. In the aortic root, the distribution of total EPA level and cholesteryl esters containing EPA followed a concentration gradient from the vascular endothelium to the media. In the aortic arch, free EPA and 12-hydroxy-EPA colocalized with M2 macrophage.
Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.
n-3 多不饱和脂肪酸，特别是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），对动脉粥样硬化有有益的影响。虽然已经报道了具体的有益作用，但 n-3 多不饱和脂肪酸在斑块中的详细分布及其在疾病进展中的相关性尚不清楚。我们的目的是评估 EPA 和 DHA 及其代谢物在动脉粥样硬化斑块中的药效学。
载脂蛋白 E 缺陷（Apoe）小鼠喂食富含 EPA（1%，w/w）或 DHA（1%，w/w）的西方饮食 3 周。对 Apoe 小鼠的主动脉根部和弓部进行了成像质谱分析，以评估 EPA、DHA、它们的代谢物以及含有 EPA 或 DHA 的脂质在斑块中的分布。还进行了液相色谱-质谱和组织学分析。含游离 EPA 和与几种脂质结合的 EPAs 的动脉粥样硬化斑块的内膜-中膜厚度减少。EPA 在薄帽斑块中的分布比在厚帽斑块中更密集，而 DHA 的分布则更均匀。在主动脉根部，总 EPA 水平和含有 EPA 的胆甾醇酯的分布遵循从血管内皮到中膜的浓度梯度。在主动脉弓部，游离 EPA 和 12-羟基-EPA 与 M2 巨噬细胞共定位。
给予的 EPA 倾向于从血管腔侧掺入，并优先进入薄帽斑块。
