APOLIPOPROTEIN B, AMPHIPHILIC BETA STRAND PEPTIDES, AND LDL STABILITY

载脂蛋白 B、两亲性 β 链肽和 LDL 稳定性

• 批准号: 3779779
• 金额: --
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3779779
• 关键词: amphiphilicity; apolipoproteins; artery; atherosclerosis; chemical binding; chemical kinetics; chickens; chromatography; collagen; elastin; electron microscopy; gel electrophoresis; hyperlipidemia; immunologic assay /test; laboratory rabbit; laboratory rat; low density lipoprotein; monoclonal antibody; peptides; thermodynamics

An early event in atherogenesis is accumulation of LDL in the artery wall in association with extracellular matrix (ECM). LDL sequestered on ECM is prone to oxidation and other modifications. LDL may also be modified within the circulation. The central hypotheses of this proposal are: 1. Apolipoprotein B stabilizes the LDL surface; thus conditions which lower the surface concentration of apo B (e.g., certain hyperlipemias where LDL radius increases without a concommitant increase in protein) or disrupt the structure and integrity of apo B (e.g., oxidation) can destabilize LDL. 2. The instability of LDL can lead to: a. Homogeneous fusion of LDL. Such fusion has been reported to lead to foam cell formation. b. Heterogeneous fusion of LDL with hydrophobic sites, such as collagens and elastins of artery wall ECM. The specific aims of this proposal are to examine both thermodynamic and kinetic aspects of LDL fusion. In particular: 1. To test the hypothesis that hyperlipemic and oxidized LDL are more prone to homogeneous fusion than are normal LDL. 2. To test the contribution of increased interfacial tension and altered surface charge to the process of homogeneous fusion. 3. To determine whether adsorption of amphiphilic beta strand peptides to hyperlipemic and oxidized LDL inhibits homogeneous fusion. 4. To test the hypothesis that hyperlipemic and oxidized LDL are more prone to heterogeneous fusion to ECM proteins than are normal LDL. Collagens will be used as the prototype of ECM proteins, these studies will then be extended to elastin.

动脉粥样硬化形成的早期事件是低密度脂蛋白在动脉壁中的积累 与细胞外基质（ECM）相关。 隔离在 ECM 上的 LDL 是 容易发生氧化和其他修饰。 LDL也可能被修改 循环内。 该提案的中心假设是： 1.载脂蛋白B稳定LDL表面；因此条件 降低载脂蛋白 B 的表面浓度（例如，某些高脂血症，其中 低密度脂蛋白半径增加但蛋白质不随之增加）或破坏 apo B 的结构和完整性（例如氧化）可能会破坏 LDL 的稳定性。 2. LDL的不稳定性会导致： 一个。 LDL 的同质融合。 据报道，这种融合导致 泡沫细胞的形成。 b. LDL 与疏水位点（例如胶原蛋白）的异质融合 和动脉壁 ECM 的弹性蛋白。 该提案的具体目标是检查热力学和 LDL 融合的动力学方面。 尤其： 1. 检验高脂血症和氧化 LDL 更重要的假设 比正常 LDL 更容易发生同质融合。 2. 测试界面张力增加和改变的贡献 表面电荷对均匀熔化过程的影响。 3. 确定两亲性β链肽是否被吸附 高脂血症和氧化的低密度脂蛋白会抑制同质融合。 4. 检验高脂血症和氧化 LDL 更重要的假设 与正常 LDL 相比，更容易与 ECM 蛋白发生异质融合。 胶原蛋白将被用作 ECM 蛋白的原型，这些研究将 然后扩展到弹性蛋白。