Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

Inhibitor sensitivity of human serum and vascular semicarbazide-sensitive amine oxidases.

Recent data suggest that elevated serum semicarbazide-sensitive amine oxidase activity (SSAO) may cause endothelial injury. Formation of cytotoxic metabolites (especially formaldehyde) and increased oxidative stress might lead to initiation or progression of atherosclerosis. Effective and selective inhibitors of human SSAO might exert cytoprotective effect on endothelial cells. To compare the inhibitor sensitivity of human serum and vascular tissue SSAO enzyme, the inhibitory effect of semicarbazide and MDL 72974A was investigated. Serum and vascular SSAO activity has been determined using 14C-benzylamine as a substrate. The IC50 values of semicarbazide were estimated to be 5x10(-3) M and 5x10(-4) M for SSAO from human serum and saphenous vein, respectively. MDL 72974A amine oxidase inhibitor was more than thousand times more effective than semicarbazide. The IC50 values were 10(-7) M and 10(-8) M for SSAO from human serum and saphenous vein, respectively. This finding supports the hypothesis that soluble and membrane-bound vascular SSAO enzymes might have similar structure.