Ditiatkovski Michael, Palsson Jonatan, Chin-Dusting Jaye, Remaley Alan T, Sviridov Dmitri
From the Laboratory of Lipoproteins and Atherosclerosis, Baker Heart and Diabetes Institute, Melbourne, Australia (M.D., J.P., D.S.); Department of Pharmacology, Monash University, Melbourne, Australia (J.C.-D.); and Lipoprotein Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (A.T.R.).
Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):1301-1306. doi: 10.1161/ATVBAHA.117.309523. Epub 2017 May 18.
Apolipoprotein A-I (apoA-I) mimetic peptides have antiatherogenic properties of high-density lipoprotein in vitro and have been shown to inhibit atherosclerosis in vivo. It is unclear, however, if each in vitro antiatherogenic property of these peptides translates to a corresponding activity in vivo, and if so, which of these contributes most to reduce atherosclerosis.
The effect of 7 apoA-I mimetic peptides, which were developed to selectively reproduce a specific component of the antiatherogenic properties of apoA-I, on the development of atherosclerosis was investigated in apolipoprotein E-deficient mice fed a high-fat diet for 4 or 12 weeks. The peptides include those that selectively upregulate cholesterol efflux, or are anti-inflammatory, or have antioxidation properties. All the peptides studied effectively inhibited the in vivo development of atherosclerosis in this model to the same extent. However, none of the peptides had the same selective effect in vivo as they had exhibited in vitro. None of the tested peptides affected plasma lipoprotein profile; capacity of plasma to support cholesterol efflux was increased modestly and similarly for all peptides.
There is a discordance between the selective in vitro and in vivo functional properties of apoA-I mimetic peptides, and the in vivo antiatherosclerotic effect of apoA-I-mimetic peptides is independent of their in vitro functional profile. Comparing the properties of apoA-I mimetic peptides in plasma rather than in the lipid-free state is better for predicting their in vivo effects on atherosclerosis.
载脂蛋白A-I（apoA-I）模拟肽在体外具有高密度脂蛋白的抗动脉粥样硬化特性，且已证实在体内可抑制动脉粥样硬化。然而，尚不清楚这些肽的每种体外抗动脉粥样硬化特性是否能转化为体内相应的活性，若能转化，其中哪种特性对减轻动脉粥样硬化的作用最大。
研究了7种apoA-I模拟肽对动脉粥样硬化发展的影响，这些肽旨在选择性重现apoA-I抗动脉粥样硬化特性的特定成分，研究对象为喂食高脂饮食4周或12周的载脂蛋白E缺陷小鼠。这些肽包括选择性上调胆固醇流出的肽、具有抗炎作用的肽或具有抗氧化特性的肽。在此模型中，所有研究的肽均能有效抑制动脉粥样硬化的体内发展，且程度相同。然而，没有一种肽在体内具有与体外相同的选择性作用。所测试的肽均未影响血浆脂蛋白谱；所有肽使血浆支持胆固醇流出的能力均适度且相似地增加。
apoA-I模拟肽的体外和体内选择性功能特性之间存在不一致，且apoA-I模拟肽的体内抗动脉粥样硬化作用与其体外功能特性无关。相较于在无脂状态下，在血浆中比较apoA-I模拟肽的特性更有助于预测它们对动脉粥样硬化的体内作用。
