BACKGROUND Oxidation of small dense low-density lipoprotein (sdLDL) and membranes is causally related to atherosclerosis. The omega-3 fatty acid (FA) eicosapentaenoic acid (EPA, 20:5, ω-3) significantly reduced oxidized LDL in patients with hypertriglyceridemia by unknown mechanisms. We compared EPA effects to related FAs of varying chain length and unsaturation on oxidation of sdLDL and model membranes, and on cholesterol crystal domains. We compared EPA to the FAs: stearic (SA, 18:0), oleic (OA, 18:1, ω-9), linoleic (LA, 18:2, ω-6), alpha-linolenic (ALA, 18:3, ω-3), eicosanoic (EA, 20:0), eicosatrienoic (ETE, 20:3, ω-3), arachidonic (AA, 20:4, ω-6), docosapentaenoic (DPA, 22:5, ω-3), and docosahexaenoic (DHA, 22:6, ω-3). METHODS Human sdLDL or model membranes of cholesterol and 1,2-Dilinoleoyl-sn-glycero-3-phosphocholine [18:2(cis)PC or DLPC] were preincubated with FAs followed by copper-induced oxidation. Malondialdehyde (MDA) or lipid hydroperoxides (LOOH) levels measured oxidation; small-angle X-ray diffraction assessed cholesterol domain formation. RESULTS After 40 min, EPA reduced MDA levels 70% compared to vehicle (p < 0.001). Lesser inhibition was observed with DHA, DPA, ETE, and ALA (33%, 34%, 32%, and 16%, respectively; all p < 0.001 versus vehicle). Similar relative FA effects were observed in model membranes where EPA more substantially inhibited cholesterol crystal domain formation. CONCLUSION We observed relationships between hydrocarbon length and unsaturation with antioxidant activity and membrane cholesterol domain formation. EPA had the most favorable molecular structure, likely contributing to membrane stability, improved lipoprotein clearance, and reduced inflammation. GENERAL SIGNIFICANCE Insight is provided into FA hydrocarbon length and unsaturation relationships with antioxidant activity in lipoproteins and membranes, and cholesterol crystal domains formation.

中文翻译：

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与体外脂肪酸相比，二十碳五烯酸（EPA）具有最佳的链长和不饱和度，可抑制小的致密LDL和膜胆固醇结构域的氧化。

背景技术小的致密的低密度脂蛋白（sdLDL）和膜的氧化与动脉粥样硬化有因果关系。Omega-3脂肪酸（FA）二十碳五烯酸（EPA，20：5，ω-3）通过未知机制显着降低高甘油三酯血症患者的氧化LDL。我们将EPA的影响与链长和不饱和度变化的相关FAs对sdLDL和模型膜的氧化以及胆固醇晶体域的氧化作用进行了比较。我们将EPA与FAs进行了比较：硬脂酸（SA，18：0），油酸（OA，18：1，ω-9），亚油酸（LA，18：2，ω-6），α-亚麻酸（ALA，18： 3，ω-3），二十烷酸（EA，20：0），二十碳三烯酸（ETE，20：3，ω-3），花生四烯酸（AA，20：4，ω-6），二十碳五烯酸（DPA，22：5， ω-3）和二十二碳六烯酸（DHA，22：6，ω-3）。方法人sdLDL或胆固醇和1,2-二亚油酰基-sn-甘油-3-磷酸胆碱的模型膜[18：将2（顺式PC或DLPC）与FAs预孵育，然后进行铜诱导的氧化。丙二醛（MDA）或脂质氢过氧化物（LOOH）含量测定氧化；小角度X射线衍射评估了胆固醇结构域的形成。结果40分钟后，EPA降低了MDA水平，与载体相比降低了70％（p <0.001）。用DHA，DPA，ETE和ALA观察到较小的抑制作用（分别为33％，34％，32％和16％；相对于赋形剂，所有p <0.001）。在模型膜中观察到了类似的相对FA效应，其中EPA更充分地抑制了胆固醇晶体结构域的形成。结论我们观察到碳氢化合物长度和不饱和度与抗氧化剂活性和膜胆固醇结构域形成之间的关系。EPA的分子结构最有利，可能有助于膜的稳定性，改善脂蛋白清除率，减少炎症。一般意义深入了解FA烃的长度和不饱和关系，以及脂蛋白和膜中的抗氧化剂活性以及胆固醇晶体结构域的形成。