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.

动脉粥样硬化中的早期事件是LDL在动脉壁中的积累 与细胞外基质（ECM）相关。 在ECM上隔离的LDL是 容易氧化和其他修饰。 LDL也可以修改 在循环中。 该提议的中心假设是： 1。载脂蛋白B稳定LDL表面；因此条件 降低apo b的表面浓度（例如，某些高脂症，其中 LDL半径增加而没有蛋白质的同时增加或破坏 APO B（例如氧化）的结构和完整性可能破坏LDL的稳定。 2。LDL的不稳定性可能导致： 一个。 LDL的均匀融合。 据报道，这种融合会导致 泡沫细胞形成。 b。 LDL与疏水位点的异质融合，例如胶原蛋白 和动脉壁ECM的弹性蛋白。 该提案的具体目的是检查热力学和 LDL融合的动力学方面。 尤其： 1。检验假说，高脂和氧化的LDL更多 比正常LDL容易融合。 2。测试增加界面张力的贡献并改变 表面电荷到均匀融合的过程。 3。确定两亲β链肽的吸附是否 高脂和氧化的LDL抑制均匀融合。 4。测试高脂和氧化的LDL的假设更多 与正常LDL相比，与ECM蛋白异质融合的异质融合。 胶原蛋白将用作ECM蛋白的原型，这些研究将 然后扩展到弹性蛋白。