Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Immune Microenvironment and Disease-Ministry of Education, Department of Physiology and Pathophysiology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, QiXiangTai Road 23, Tianjin 300070, China; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, PingJiang Road 22, Tianjin, 300211, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, PingJiang Road 22, Tianjin, 300211, China.
Clin Nutr. 2021 Feb;40(2):445-459. doi: 10.1016/j.clnu.2020.05.034. Epub 2020 Jun 18.
BACKGROUND & AIMS: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) have been reported to have beneficial cardiovascular effects, but its mechanism of protection against acute myocardial infarction (AMI) who are under guideline-based therapy is not fully understood. Here, we used a metabolomic approach to systematically analyze the eicosanoid metabolites induced by ω-3 PUFA supplementation and investigated the underlying mechanisms.
Participants with AMI after successful percutaneous coronary intervention were randomized to 3 months of 2 g daily ω-3 PUFA and guideline-adjusted therapy (n = 30, ω-3 therapy) or guideline-adjusted therapy alone (n = 30, Usual therapy). Functional PUFA-derived eicosanoids in plasma were profiled by metabolomics. Clinical and laboratory tests were obtained before and 3 months after baseline and after the study therapy.
By intent-to-treat analysis, the content of 11-HDoHE, 20-HDoHE and 16,17-EDP and that of epoxyeicosatetraenoic acids (EEQs), derived from docosahexaenoic acid and eicosapentaenoic acid, respectively, were significantly higher with ω-3 group than Usual therapy, whereas that of prostaglandin J2 (PGJ2) and leukotriene B4, derived from arachidonic acid, was significantly decreased. As compared with Usual therapy, ω-3 PUFA therapy significantly reduced levels of triglycerides (-6.3%, P < 0.05), apolipoprotein B (-4.9%, P < 0.05) and lipoprotein(a) (-37.0%, P < 0.05) and increased nitric oxide level (62.2%, P < 0.05). In addition, the levels of these variables were positively correlated with change in 16,17-EDP and EEQs content but negatively with change in PGJ2 content.
ω-3 PUFA supplementation may improve lipid metabolism and endothelial function possibly by affecting eicosanoid metabolic status at a systemic level during convalescent healing after AMI.
URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1900025859.
已报道称ω-3 多不饱和脂肪酸（ω-3 PUFA）具有有益的心血管作用，但在遵循指南治疗的情况下，其对急性心肌梗死（AMI）的保护机制尚不完全清楚。在这里，我们使用代谢组学方法系统分析 ω-3 PUFA 补充诱导的类二十烷酸代谢物，并探讨其潜在机制。
成功行经皮冠状动脉介入治疗后的 AMI 患者被随机分为 3 个月每日 2g ω-3 PUFA 和指南调整治疗（n=30，ω-3 治疗组）或单独进行指南调整治疗（n=30，常规治疗组）。通过代谢组学对血浆中功能性 PUFA 衍生的类二十烷酸进行分析。在基线和研究治疗后 3 个月，分别进行临床和实验室检查。
意向治疗分析显示，ω-3 治疗组 11-HDoHE、20-HDoHE 和 16,17-EDP 的含量以及分别来源于二十二碳六烯酸和二十碳五烯酸的环氧二十碳三烯酸（EEQs）的含量明显高于常规治疗组，而来源于花生四烯酸的前列腺素 J2（PGJ2）和白三烯 B4 的含量明显降低。与常规治疗组相比，ω-3 PUFA 治疗组三酰甘油水平（-6.3%，P<0.05）、载脂蛋白 B（-4.9%，P<0.05）和脂蛋白（a）（-37.0%，P<0.05）降低，一氧化氮水平升高（62.2%，P<0.05）。此外，这些变量的水平与 16,17-EDP 和 EEQs 含量的变化呈正相关，与 PGJ2 含量的变化呈负相关。
ω-3 PUFA 补充可能通过影响 AMI 后康复期间全身水平的类二十烷酸代谢状态来改善脂质代谢和内皮功能。
