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.
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