MEASUREMENT OF GLYCATED LDL WITH MONOCLONAL ANTIBODIES

描述：（改编自申请人摘要）长期 该提案的目的是制定一个具体和准确的 免疫诊断测试，以测量非酶糖化的量， 人血浆中的低密度脂蛋白（LDL）。 测试将是ELISA 使用特异性识别 在一些实施方案中，LDL是糖基化的LDL，并且不与未糖基化的LDL部分反应。 糖基化 低密度脂蛋白是血浆胆固醇的主要载体， 影响脂蛋白致动脉粥样硬化的潜力， 糖尿病患者对动脉粥样硬化并发症的易感性。 特别是，暴露于糖化LDL导致细胞内积累 胆固醇酯，损害LDL的生理能力， 通过LDL受体途径代谢，并通过替代途径促进摄取 受体导致巨噬细胞形态转化为泡沫 细胞 因此，血浆或血清中糖化LDL的测量可以是 在糖尿病患者中具有重要的诊断和治疗意义 糖尿病。 然而，除了耗时、繁琐和经常 目前，仅适用于研究实验室的方法不足， 没有可靠和方便的方法来估计糖化LDL 临床样品中的浓度。 一种简单而特异的方法， 测量血浆中的糖化低密度脂蛋白不仅是因为它有可能作为一种 糖尿病患者动脉粥样硬化形成的诊断指标， 用作糖尿病患者长期随访的可重复参数 人群，以评估与升高相关的预测价值和风险 糖化LDL水平。 这个项目将利用我们最近的可证明的 成功地创造了独特的和高度特异性的单克隆抗体， 识别LDL载脂蛋白中的糖化表位，但不识别其他蛋白中的糖化表位。 血浆蛋白，不与未糖化的LDL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.