Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03823, USA; Elucida Research LLC, Beverly, MA 01915-0091, USA.
Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115-6110, USA.
Prostaglandins Leukot Essent Fatty Acids. 2022 Jul;182:102450. doi: 10.1016/j.plefa.2022.102450. Epub 2022 May 21.
The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.
ω-3 脂肪酸（n3-FAs），如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），能够迅速融入细胞膜，调节信号转导途径、脂筏形成和胆固醇分布。细胞膜上的 n3-FAs 还能形成特殊的促分解介质和其他细胞内的氧化脂类，调节炎症途径，包括 T 细胞分化和基因表达。心血管（CV）临床试验表明，二十碳五烯酸乙酯（IPE）作为 EPA 的一种给药形式，可以减少他汀类药物治疗的高危患者的复合 CV 事件和斑块体积。混合 EPA/DHA 方案并未显示出这些益处，这可能是由于配方、剂量或 DHA 的潜在代偿作用的差异。事实上，EPA 和 DHA 对膜的结构组织和细胞功能具有独特的、组织特异性的影响。这篇综述总结了：（1）使用 n3-FA 制剂的临床结果和影像学试验结果；（2）n3-FAs 的膜相互作用；（3）n3-FAs 在高血糖期间对膜氧化应激和胆固醇结晶域形成的影响；（4）n3-FAs 对内皮功能的影响；（5）n3-FA 生成的代谢物在炎症中的作用；以及（6）正在进行和未来的临床研究，探索 n3-FAs 的治疗靶点，包括 COVID-19。
