Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia
Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia
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DOI：
10.1016/j.atherosclerosis.2014.10.011
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发表时间：
2014-12-01
期刊：
影响因子：
5.3
通讯作者：
Hirata, Ken-ichi
中科院分区：
文献类型：
--
作者：
Tanaka, Nobuaki;Ishida, Tatsuro;Hirata, Ken-ichi
目的：有报道称，高密度脂蛋白（HDL）在病理条件下丧失抗炎功能并促进动脉粥样硬化。然而，目前还没有改善HDL功能的药物治疗。我们的目的是评估口服二十碳五烯酸（EPA）对HDL功能的影响。研究方法：日本血脂异常患者接受EPA（1800 mg/天，4周）治疗，并利用体外细胞分析评估HDL的抗炎功能。结果如下：EPA治疗没有改变血清胆固醇和甘油三酯水平，但它显着增加EPA浓度的血清和HDL组分。HDL中的EPA/花生四烯酸比例与血清中的比例成比例，表明口服施用的EPA有效地掺入HDL颗粒中。EPA处理后的HDL显示出抗氧化酶对氧磷酶-1的活性显著增加。此外，EPA-丰富的HDL显着改善内皮细胞迁移，并显着抑制血管细胞粘附分子-1的表达，在人脐静脉内皮细胞中，与EPA治疗前的HDL相比。此外，富含EPA的HDL增强了巨噬细胞的胆固醇流出能力。结论：口服EPA可恢复HDL的抗氧化和抗炎功能，并促进巨噬细胞胆固醇流出。因此，对于有冠状动脉危险因素的患者，EPA可能会将“功能失调的HDL”转化为“功能失调的HDL”。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Objective: It has been reported that high-density lipoprotein (HDL) loses anti-inflammatory function and promotes atherosclerosis under pathological conditions. However, no pharmacological therapy to improve HDL function is currently available. We aimed to evaluate the effect of oral administration of eicosapentaenoic acid (EPA) on HDL function. Methods: Japanese patients with dyslipidemia were treated with EPA (1800 mg/day, 4 weeks), and anti-inflammatory functions of HDL were assessed utilizing in vitro cell-based assays. Results: The EPA treatment did not change serum cholesterol and triglyceride levels, but it significantly increased EPA concentrations in the serum and HDL fraction. The EPA/ arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that the orally administered EPA was efficiently incorporated into the HDL particles. The HDL after EPA treatment showed significantly increased activity of anti-oxidative enzyme, paraoxonase-1. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1, in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL augmented cholesterol efflux capacity from macrophages. Conclusion: Oral administration of EPA regenerated anti-oxidative and anti-inflammatory functions of HDL, and promoted cholesterol efflux from macrophages. Therefore, EPA may transform "dysfunctional HDL" to "functional", in patients with coronary risk factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.