MEASUREMENT OF GLYCATED LDL WITH MONOCLONAL ANTIBODIES

描述：(改编自申请者摘要)长期 这项建议的目标是制定一个具体和准确的 免疫诊断试验测定非酶糖化量 人血浆低密度脂蛋白(LDL)。这项测试将是一项酶联免疫吸附试验 使用特异性识别的单抗构建 糖化的低密度脂蛋白，不与未糖化的低密度脂蛋白部分反应。糖基化 低密度脂蛋白是血浆胆固醇的主要载体，是一种结构修饰 这会影响脂蛋白的致动脉粥样硬化潜能，并且会增加 糖尿病患者对动脉粥样硬化并发症的易感性。 特别是，接触糖化低密度脂蛋白会导致细胞内积聚。 胆固醇酯的一种，使低密度脂蛋白的生理能力 通过低密度脂蛋白受体途径代谢，并通过替代促进摄取 导致巨噬细胞形态转化为泡沫的受体 细胞。因此，血浆或血清中糖化低密度脂蛋白的测量可能是 糖尿病患者的诊断和预后重要性 糖尿病。然而，除了耗时、繁琐和经常 仅适用于研究实验室的方法不足，目前有 没有可靠和方便的方法来估计糖化低密度脂蛋白 临床样本中的浓度。一种简单而具体的方法 测定血浆中的糖化低密度脂蛋白不仅是因为它作为一种潜在的 糖尿病患者动脉粥样硬化形成的诊断指标，也可用于 作为糖尿病患者长期随访的可重复性指标 评估与升高相关的预测价值和风险的人群 糖化低密度脂蛋白水平。这个项目将利用我们最近证明的 成功地创造了独特的和高度特异的单抗 识别存在于载脂蛋白中的糖化表位，但不识别其他 血浆蛋白，不与未糖化的低密度脂蛋白反应。

DESCRIPTION: (Adapted from the applicants abstract) The long-term objective of this proposal is to develop a specific and accurate immunodiagnostic test to measure the amount of non-enzymatically glycated low density lipoprotein (LDL) in human plasma. The test will be an ELISA construct that employs monoclonal antibody that specifically recognize glycated LDL, and do not react with unglycated LDL moieties. Glycation of LDL, the major carrier of plasma cholesterol, is a structural modification that affects the atherogenic potential of lipoproteins, and that increases the susceptibility of diabetic subjects to atherosclerotic complications. In particular, exposure to glycated LDL leads to intracellular accumulation of chlesterol esters, compromises the physiological ability of LDL to be metabolized by the LDL receptor pathway, and promotes uptake by alternative receptors leading to morphologic transformation of macrophages into foam cells. Thus, measurement of glycated LDL in plasma or serum may be diagnostically and prognostically important in patients with diabetes mellitus. However, aside from time consuming, cumbersome and often inadequate methods suitable only for research laboratories, there currently are no reliable and convenient means to estimating glycated LDL concentrations in clinical samples. A simple and specific method for measuring glycated LDL in plasma is needed not only for its potential as a diagnostic indicator of atherogenesis in diabetic individuals, but also for use as a reproducible parameter for long term follow up in diabetic populations to asses the predictive value and risk associated with elevated levels of glycated LDL. This project will exploit our recent demonstrable success in creating unique and highly specific monoclonal antibodies that recognize glycated epitopes residing in LDL apoprotein but not in other plasma proteins and that do not react with unglycated LDL.