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首页> 外文期刊>Current Science: A Fortnightly Journal of Research >Toward the design of peptide mimics of antiatherogenic apolipoproteins A-Iand E
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Toward the design of peptide mimics of antiatherogenic apolipoproteins A-Iand E

机译：设计抗动脉粥样化载脂蛋白A-I和E的肽模拟物

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摘要

Two major markers for atherosclerosis are increased plasma cholesterol levels and low levels of high density lipoproteins (HDL). Human apolipoprotein (apo) A-I, the major protein component of HDL, has been shown to inhibit atherosclerosis in vivo without altering plasma cholesterol levels, perhaps through its antioxidant effect on low density lipoproteins (LDL). On the other hand, apo E inhibits atherosclerosis by enhancing the uptake of atherogenic lipoproteins by the liver and thus lowering plasma cholesterol levels. The class A amphipathic peptide 18A (DWLKAFYDKVAEKLKEAF) and its analogues, designed based on the lipid-associating amphipathic helical motif present in apo A-I, have been shown by us to mimic properties of apo A-I, Recently, we have shown that administration of an analogue of 18A was also able to inhibit atherosclerosis in atherosclerosis-sensitive mice, similar to apo A-I, without altering the plasma cholesterol levels, Based on the presence of two domains in apo E, the lipid-associating domain and the receptor-binding cationic domain, linking residues 141-150 of apo E to 18A resulted in a peptide that enhanced the uptake of atherogenic lipoproteins in vitro. Administration of this peptide into dyslipidemic mice showed a dramatic decrease in plasma cholesterol levels, These results demonstrate the potential for the design of peptides to ameliorate atherosclerosis, the number one cause of mortality in the developed countries.
机译：动脉粥样硬化的两个主要标志是血浆胆固醇水平升高和高密度脂蛋白（HDL）水平降低。人类载脂蛋白（apo）A-I是HDL的主要蛋白成分，已显示出可以在不改变血浆胆固醇水平的情况下抑制体内动脉粥样硬化，这可能是由于其对低密度脂蛋白（LDL）的抗氧化作用。另一方面，载脂蛋白E通过增强肝脏对动脉粥样硬化脂蛋白的吸收并因此降低血浆胆固醇水平来抑制动脉粥样硬化。基于apo AI中存在的与脂质相关的两亲性螺旋基序设计的A类两亲肽18A（DWLKAFYDKVAEKLKEAF）及其类似物已被我们证明可模仿apo AI的特性。最近，我们证明了类似物的给药类似于apo AI，18A中的A也能够在不改变血浆胆固醇水平的情况下，在对动脉粥样硬化敏感的小鼠中抑制动脉粥样硬化，基于apo E中存在两个域，即脂质结合域和受体结合阳离子域，将载脂蛋白E的141-150残基与18A连接起来，得到了一种肽，可增强体外对动脉粥样硬化脂蛋白的吸收。将该肽施用给血脂异常小鼠显示血浆胆固醇水平显着降低。这些结果证明了设计肽以改善动脉粥样硬化的潜力，动脉粥样硬化是发达国家的第一大死亡原因。

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