DECREASED EXPRESSION OF A PARTICULAR EPITOPE ON PLASMA APOLIPOPROTEIN-B OF PATIENTS WITH CORONARY-ARTERY DISEASE

Plasma low density lipoproteins (LDL) of patients with coronary artery disease (CAD) may be qualitatively different from those of normal persons. To study the immunochemical difference in plasma LDL between CAD patients and normals, we employed competitive enzyme-linked immunosorbent assay (ELISA) using one polyclonal and five monoclonal anti-LDL antibodies to measure apolipoprotein B (apo B) epitope expression in whole plasma from 20 angiographically documented CAD patients and 7 healthy control subjects. The patient group had a significantly higher plasma concentration of apo B but showed decreased relative expression of the 4B11 epitope in plasma LDL. No significant difference in the expression of the other four epitopes was found between patients and controls. The 4B11 monoclonal anti-LDL antibody was demonstrated to inhibit the modification of native LDL by endothelial cells (EC) and to reduce subsequent uptake and degradation by J774 macrophages. In vitro oxidative modification of LDL by EC or Cu2+ was associated with a decrease in the 4B11 immunoreactivity on apo B. The results imply that plasma LDL may be somewhat oxidatively modified in vivo by vascular endothelium in patients with CAD. Competitive inhibition assay further showed that plasma LDL of CAD patients had greater ability to compete for scavenger receptor and less ability to compete for LDL receptor of J774 macrophages than those of controls. Pretreatment of EC with plasma LDL of CAD patients as compared to those of control subjects induced a significantly greater increase in U937 monocyte adhesion. In conclusion, plasma LDL of CAD patients demonstrated decreased expression of a particular apo B epitope related to scavenger receptor-binding site of EC-modified LDL and greater affinity for scavenger receptor, and caused enhanced adherence of monocytes to EC. The data support the existence of qualitative changes in plasma LDL of CAD patients.