LDL

低密度脂蛋白

• 批准号: 7951449
• 负责人: WALTER P BLAND
• 金额: $ 2.03万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951449
• 关键词: Adverse effects; Alcoholic beverage heavy drinker; Binding; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Coronary artery; Funding; Genes; Genetic Polymorphism; Grant; Heavy Drinking; Incidence; Institution; Light; Low-Density Lipoproteins; Relative (related person); Research; Research Personnel; Resources; Serum; Source; United States National Institutes of Health; Universities; alcohol exposure; drinking; macrophage; oxidized low density lipoprotein; prevent; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. LDL to oxidized LDL (OxLDL) that is rapidly taken up by macrophages leading to coronary artery diseae (CAD). Paraxonase (PON), a HDL-bound polymorphic anzyme lowers OxLDL level and thus prevents CAD. It is hypothesized that light drinking (13-40g/day) increases serum PON level and theryby lowers OxLDL by preventing its formationor by destroying it and thus has a cardioprotective effect, whereas heavy drinking (>80g/day) has the opposite side effects. The specific aims are: 1. To determine the relative concentration and activiry of the PON in light and heavy drinkers. 2. To characterize the genetic polymorphism of PON gene and correlate with the extent of alcohol exposure. 3. To determine the concentration of plasm OxLDL and correlate with their PON activity and the incidence of CAD. 4. To determine the ability of HDL's from each group to convert the biologically active oxidized-LDL to biologically inactive form and corrlate with corresonding PON acitiviy. To determine whether anti-PON can inhibit the destruction of OxLDL by HDL's 5. To determine the ability of HDL's from each group to prvent the uptake of OxLDL by macrophages and correlate with the corresponding PON activity. To determin where Anti-PON can specifically block the protective effecgt of HDL's.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 LDL转化为氧化LDL OxLDL，被巨噬细胞迅速吸收，导致冠状动脉疾病CAD。副轴突酶PON是一种HDL结合的多态性酶，可降低OxLDL水平，从而预防CAD。据推测，少量饮酒13- 40克/天可增加血清PON水平，从而通过阻止其形成或破坏其来降低OxLDL，从而具有心脏保护作用，而大量饮酒80克/天则具有相反的副作用。具体目标是： 1.测定轻度和重度饮酒者血清PON的相对浓度和活性。 2.探讨PON基因多态性与酒精暴露程度的关系。 3.测定冠心病患者血浆氧化低密度脂蛋白（OxLDL）浓度，并探讨其与PON活性及冠心病发病率的相关性。 4.测定各组高密度脂蛋白（HDL）将生物活性的氧化低密度脂蛋白（LDL）转化为生物活性的低密度脂蛋白（LDL）的能力，并与相应的PON活性相关。为了确定抗PON是否能抑制HDL对OxLDL的破坏， 5.测定各组HDL对巨噬细胞摄取OxLDL的抑制作用，并与相应的PON活性进行相关性分析。确定抗PON在何处特异性阻断HDL的保护作用。