EVIDENCE FOR LOSS OF APO-B FROM LDL IN HUMAN ATHEROSCLEROTIC LESIONS - EXTRACELLULAR CHOLESTERYL ESTER LIPID PARTICLES LACKING APO-B

Previous studies have demonstrated the accumulation of low density lip oprotein (LDL) in the extracellular spaces of the intima of normal and atherosclerotic human vessels. In this study we have assessed the deg ree of colocalization in vessels of apolipoprotein B (apo B), the majo r protein of LDL, with cholesteryl ester, the predominant lipid of LDL . Apo B was detected immunohistochemically and cholesteryl ester was d etected after its enzymatic hydrolysis and staining with the fluoresce nt probe, filipin. Most normal intima showed apo B staining without as sociated cholesteryl ester staining. This result would be expected wit h LDL having intact apo B; intact apo B interferes with hydrolysis and filipin staining of LDL cholesteryl ester. Fatty streaks and fibrous plagues showed regions of congruent apo B and cholesteryl ester staini ng in the extracellular space, suggesting fragmentation of apo B witho ut loss of its immunoreactivity. Still other areas of lesions showed c holesteryl ester staining in the extracellular space without apo B sta ining. This staining pattern suggests loss of apo B from LDL leaving o nly the cholesteryl ester-rich core of LDL. Progressive loss of apo B from LDL can explain the patterns of apo B and cholesteryl ester coloc alization that occur in vessel wall intima. The distribution of these patterns in normal and atherosclerotic lesions suggests that loss of a po B from the cholesteryl ester core of LDL is associated with lesion development.