Development of Apo Mimetic Peptides for the Treatment Cardiovascular Disease

5A两亲性多肽，早些时候被我们的实验室证明是专门用于通过ABCA1转运蛋白去除胆固醇的，在过去的一年里在几个动物模型中进行了测试。在兔项圈模型上，5A肽被发现能减少内皮细胞上黏附分子的表达，并减少炎症细胞向血管壁的渗透。当小鼠接受单次静脉注射5A肽治疗时，它提高了高密度脂蛋白-C，并增加了血清从细胞中清除多余胆固醇的能力。此外，还发现5A肽可以动员周围组织中的胆固醇，并增加粪便中胆固醇的排泄。长期使用该多肽可显著减轻载脂蛋白E基因敲除小鼠的动脉粥样硬化，表明该多肽可能是使用载脂蛋白A-I进行高密度脂蛋白输注治疗的一种可能的替代方法。对一类被称为麋鹿肽的两亲性多肽的结构-功能研究表明，某些结构基序与它们的体外生物学特性有关。在未来，将比较麋鹿多肽的体外性质和它们对小鼠动脉粥样硬化模型的影响，为载脂蛋白模拟多肽的设计提供更好的理论基础。

The 5A amphipathic peptide, which was shown earlier by our laboratory to be specific for removing cholesterol by the ABCA1 transporter, was tested in the past year in several animal models. Using a rabbit collar model, the 5A peptide was found to reduce the expression of adhesion molecules on endothelial cells and reduce the infiltration of inflammatory cells into the vessel wall. When mice were treated with a single IV bolus of the 5A peptide, it raised HDL-C and increased the capacity of serum for removing excess cholesterol from cells. Furthermore, the 5A peptide was found to mobilize cholesterol from peripheral tissues and increase fecal cholesterol excretion. Long term treatment of the peptide was found to markedly reduce atherosclerosis in apoE knokout mice, indicating that it may be a possible alternative to using apolipoprotein A-I for HDL infusion therapy. Structure-function studies of a family of amphipathic peptides referred to as ELK peptides revealed that certain structural motifs correlated with their in vitro biological properties. In the future, the in vitro properties of the ELK peptides will be compared to their effect on mouse models of atherosclerosis to provide a better rationale in the design of apolipoprotien mimetic peptides.