Development of Apo Mimetic Peptides for the Treatment Cardiovascular Disease

5A两亲性肽，这是由我们的实验室早些时候被证明是特定的清除胆固醇的ABCA 1转运蛋白，在过去的一年中，在几个动物模型进行了测试。 使用兔项圈模型，发现5A肽减少内皮细胞上粘附分子的表达，并减少炎性细胞向血管壁的浸润。 当小鼠接受5A肽的单次静脉推注治疗时，它提高了HDL-C，并增加了血清从细胞中去除多余胆固醇的能力。 此外，发现5A肽从外周组织动员胆固醇并增加粪便胆固醇排泄。 在apoE基因敲除小鼠中，发现肽的长期治疗显著减少动脉粥样硬化，表明它可能是使用载脂蛋白A-I进行HDL输注治疗的可能替代方案。 对ELK肽家族的结构-功能研究表明，某些结构基序与其体外生物学特性相关。 在未来，ELK肽的体外特性将与它们对动脉粥样硬化小鼠模型的作用进行比较，以在载脂蛋白模拟肽的设计中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.