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首页> 外文期刊>Circulation research: a journal of the American Heart Association >Structure/function relationships of apolipoprotein a-I mimetic peptides: implications for antiatherogenic activities of high-density lipoprotein.
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Structure/function relationships of apolipoprotein a-I mimetic peptides: implications for antiatherogenic activities of high-density lipoprotein.

机译：载脂蛋白α-I模拟肽的结构/功能关系：对高密度脂蛋白抗动脉粥样硬化活性的影响。

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RATIONALE: Apolipoprotein (apoA)-I mimetic peptides are a promising type of anti-atherosclerosis therapy, but how the structural features of these peptides relate to the multiple antiatherogenic functions of HDL is poorly understood. OBJECTIVE: To establish structure/function relationships of apoA-I mimetic peptides with their antiatherogenic functions. METHODS AND RESULTS: Twenty-two bihelical apoA-I mimetic peptides were investigated in vitro for the capacity and specificity of cholesterol efflux, inhibition of inflammatory response of monocytes and endothelial cells, and inhibition of low-density lipoprotein (LDL) oxidation. It was found that mean hydrophobicity, charge, size of hydrophobic face, and angle of the link between the helices are the major factors determining the efficiency and specificity of cholesterol efflux. The peptide with optimal parameters was more effective and specific toward cholesterol efflux than human apoA-I. Charge and size of hydrophobic face were also the major factors affecting antiinflammatory properties, and the presence of cysteine and histidine residues was the main factor determining antioxidant properties. There was no significant correlation between capacities of the peptides to support individual functions; each function had its own optimal set of features. CONCLUSIONS: None of the peptides was equally effective in all the antiatherogenic functions tested, suggesting that different functions of HDL may have different mechanisms and different structural requirements. The results do suggest, however, that rationalizing the design of apoA-I mimetic peptides may improve their therapeutic value and may lead to a better understanding of mechanisms of various antiatherogenic functions of HDL.
机译：原理：载脂蛋白（apoA）-I模拟肽是一种有前途的抗动脉粥样硬化疗法，但人们对这些肽的结构特征与HDL的多种抗动脉粥样硬化功能之间的关系知之甚少。目的：建立具有抗动脉粥样硬化作用的apoA-I模拟肽的结构/功能关系。方法和结果：体外研究了二十二种双螺旋apoA-I模拟肽的胆固醇外排能力和特异性，抑制单核细胞和内皮细胞的炎症反应以及抑制低密度脂蛋白（LDL）氧化。已经发现，平均疏水性，电荷，疏水性表面的大小以及螺旋之间的连接角是决定胆固醇外排效率和特异性的主要因素。具有最佳参数的肽比人apoA-I更有效且对胆固醇流出具有特异性。疏水性面部的电荷和大小也是影响抗炎特性的主要因素，半胱氨酸和组氨酸残基的存在是决定抗氧化特性的主要因素。肽支持个体功能的能力之间没有显着相关性。每个功能都有其自己的最佳功能集。结论：在所有测试的抗动脉粥样硬化功能中，没有一种肽具有同样的效果，这表明不同的HDL功能可能具有不同的机制和不同的结构要求。然而，结果确实表明，合理化apoA-I模拟肽的设计可能会提高其治疗价值，并可能导致人们更好地理解HDL的多种抗动脉粥样硬化功能的机制。

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