Immunodetection of modified lipoproteins in plasma and arterial walls of patients with coronary heart disease.

Data from literature indicate that immune processes play an important role in atherogenesis. Modified lipoproteins might be immunogenic and generate autoantibodies in plasma. To determine whether the level of such circulating autoantibodies correlates with the extent of atherosclerosis expressed as cholesterol values in plasma (C), very low density (VLDL-C), low density (LDL-C), and high density lipoproteins (HDL-C), we compared the level of plasma autoantibodies of a group of coronary heart disease patients (CHD-P) with that of normal, age-matched donors, with no history of cardiac disease (N). All CHD-P (even normocholesterolemic) were characterized by an LDL-C/HDL-C ratio > 4, while all N (even hypercholesterolemic) had this ratio < 4. A double level of circulating autoantibodies against VLDL and LDL in CHD-P as compared to N group was detected. The anti-LDL antibodies level correlated well with LDL-C level and was negatively correlated with the age of patients. For tissue localization of native and modified LDL (as well as other possibly modified proteins) we used immunohistochemical techniques, employing antihuman LDL, antihydroxynonenal-lysine (HNE-Lys), and antiadvanced glycation end-products (AGE) proteins. Antibodies were applied on consecutive cryosections of the aortic arch, valves and coronary arteries of CHD-P. The immunodetected antigens were colocalized in focal deposits, in the cap and shoulders of the atheroma. Native LDL and modified proteins (AGE, HNE-Lys) were detected either diffuse-extracellularly or associated with macrophage-derived foam cells and smooth muscle cells of the intima. These data indicate the following: a) the existence of an elevated level of circulating autoantibodies against VLDL and LDL, which correlates negatively with the age of CHD patients; b) the presence of LDL (possibly glycated or oxidized) in detectable amounts in the intima of atherosclerosis-affected arteries; c) the modified lipoproteins are immunoactive components in the atherosclerotic process.