Immunochemical studies of malondialdehyde-altered macromolecules in cholesterol-fed New Zealand white rabbits.
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PublisherThe University of Arizona.
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AbstractMalondialdehyde (MDA), a product of lipid peroxidation and arachidonic acid metabolism, can react with free amino groups to form crosslinks which may form neoantigens and result in autoantibody production. Under hyperlipidemic conditions, excess MDA produced endogenously could conjugate with proteins to generate new antigenic sites, new antigenic sites could stimulate autoantibody production resulting in immune complex formation leading to complement activation and tissue damage. This study was designed to develop an immunological assays to determine whether the presence of plasma MDA-modified proteins existed and to study a time-course relationship for plasma anti-MDA IgG, MDA-modified protein conjugates and circulating immune complexes containing MDA in both normal and hyperlipidemic rabbits. This study also attempts to determine whether these factors relate to the extent of atheromatous lesion development and whether immune complexes alone can accelerate the progression of atherosclerosis. An MDA-modified plasma protein (> 200 KDa) was demonstrated for the first time in rabbits by the Western blot techniques. This MDA-modified plasma protein was present in both control and cholesterol-fed rabbit plasma and its amount increased during 8 weeks of cholesterol feeding. Anti-MDA IgG antibody activity decreased over time in the control group but there was no significant decline in cholesterol-fed rabbits. Circulating immune complexes containing IgG and MDA increased in control and cholesterol-fed groups. Following injections of MDA-modified proteins, circulating immune complexes containing IgG and MDA increased significantly in rabbits fed with a normal diet but not in all cholesterol-fed rabbits. Immune complexes did not accelerate the progression of atherosclerosis. These results suggest that anti-MDA IgG may provide an immune mechanism for the normal clearance of lipid peroxidation products via circulating immune complexes and that this mechanism may be altered by a high cholesterol intake. Immunohistochemical evidence demonstrates that MDA-modified epitopes, complement C3 component and IgG are present in the atherosclerotic lesions. These results provide evidence that circulating immune reactants which involve MDA, specific autoantibodies, antigen and immune complexes may play a role in the development or progression of atherosclerosis.
Degree ProgramMicrobiology and Immunology