EFFECT OF ANTI-OXIDIZED LDL ANTIBODY MLDL 1287A ON SERUM BIOMAKERS AND INSULN RE

抗氧化 LDL 抗体 MLDL 1287A 对血清生物标志物和胰岛素抵抗的影响

• 批准号: 7958545
• 负责人: KEVIN L GROVE
• 金额: $ 8.03万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958545
• 关键词: Accounting; Affinity; Aldehydes; Antibodies; Antigen-Antibody Complex; Apolipoproteins B; Arterial Fatty Streak; Atherosclerosis; Attenuated; Autoantibodies; Binding; Blood Vessels; Cardiovascular system; Coagulants; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Diabetic Angiopathies; Disease; Event; Funding; Grant; Human; Hyperglycemia; IgG1; In Vitro; Inflammation; Inflammatory; Institution; Insulin Resistance; Length; Low-Density Lipoproteins; Macrophage Activation; Malondialdehyde; Metabolism; Morbidity - disease rate; Oryctolagus cuniculus; Pathogenesis; Patients; Primates; Process; Proteins; Quality of life; Research; Research Personnel; Resources; Serum; Serum Markers; Source; United States National Institutes of Health; cardiovascular risk factor; low density lipoprotein inhibitor; macrophage; mortality; mouse model; oxidation; 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. Cardiovascular complications account for the vast majority of the mortality and morbidity associated with diabetes (DM). These complications can be broadly categorized as macrovascular and microvascular. Microvascular complications of DM often have devastating effects on the quality of life and survival for patients with diabetes. It is now well recognized that many of microvascular complications are directly related to the degree of hyperglycemia and insulin resistance. However, our understanding of the pathogenesis and appropriate treatment of these disorders is rudimentary. Accumulation and oxidation of LDL in blood vessel walls are thought to be important factors in the process of atherosclerotic plaque formation. Upon scavenging and internalizing the oxidized LDL molecules, macrophages are activated and express pro-inflammatory molecules. The inflammatory state contributes to plaque instability and has been associated with increased risk of cardiovascular events. Presence of autoantibodies to neoepitopes on aldehyde-modified LDL have been associated with modulation of the development of atherosclerosis in rabbits and humans. MLDL1278a is a full length human IgG1 antibody which binds with high affinity to the malondialdehyde-oxidized apo-B 100 protein portion of the LDL molecule. The presence of the MLDL1278A prevents activation of macrophages upon uptake of the antigen-antibody complex in vitro, and attenuates plaque progression and induces plaque regression in a mouse model of atherosclerosis, thereby reducing the effects of inflammation on plaque development and cardiovascular events. The purpose of this study was to investigate changes in serum markers of inflammation, metabolism, and pro-coagulant activity during and following treatment with anti-oxidized LDL antibody MLDL1278A.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 心血管并发症占糖尿病(DM)相关死亡率和发病率的绝大部分。这些并发症大致可分为大血管和微血管。糖尿病的微血管并发症往往对糖尿病患者的生活质量和生存造成毁灭性的影响。现在公认的是，许多微血管并发症与高血糖和胰岛素抵抗的程度直接相关。然而，我们对这些疾病的发病机制和适当治疗的了解是初步的。 低密度脂蛋白在血管壁的积聚和氧化被认为是动脉粥样硬化斑块形成过程中的重要因素。在清除和内化氧化的低密度脂蛋白分子后，巨噬细胞被激活并表达促炎分子。炎症状态导致斑块不稳定，并与心血管事件风险增加有关。醛修饰的低密度脂蛋白上新表位的自身抗体的存在与调节兔和人的动脉粥样硬化的发展有关。MLDL1278a是一种全长的人IgG1抗体，与低密度脂蛋白分子中丙二醛氧化的apo-B100蛋白部分具有高亲和力。MLDL1278A的存在防止巨噬细胞在体外摄取抗原-抗体复合体时的激活，并在动脉粥样硬化的小鼠模型中减缓斑块进展和诱导斑块消退，从而减少炎症对斑块发展和心血管事件的影响。本研究的目的是研究抗氧化型低密度脂蛋白抗体MLDL1278A治疗前后血清炎症、代谢和促凝血活性标志物的变化。