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 lipoprotein (LDL) in the extracellular spaces of the intima of normal and atherosclerotic human vessels. In this study we have assessed the degree of colocalization in vessels of apolipoprotein B (apo B), the major protein of LDL, with cholesteryl ester, the predominant lipid of LDL. Apo B was detected immunohistochemically and cholesteryl ester was detected after its enzymatic hydrolysis and staining with the fluorescent probe, filipin. Most normal intima showed apo B staining without associated cholesteryl ester staining. This result would be expected with 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 staining in the extracellular space, suggesting fragmentation of apo B without loss of its immunoreactivity. Still other areas of lesions showed cholesteryl ester staining in the extracellular space without apo B staining. This staining pattern suggests loss of apo B from LDL leaving only the cholesteryl ester-rich core of LDL. Progressive loss of apo B from LDL can explain the patterns of apo B and cholesteryl ester colocalization that occur in vessel wall intima. The distribution of these patterns in normal and atherosclerotic lesions suggests that loss of apo B from the cholesteryl ester core of LDL is associated with lesion development.
Kruth
H S
HS
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Shekhonin
B
B
D000328:Adult; D000368:Aged; D001013:Aorta, Thoracic / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D001391:Azo Compounds; D002788:Cholesterol Esters / Q000378:metabolism*; D005372:Filipin; D006651:Histocytochemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013194:Staining and Labeling; D017539:Tunica Intima / Q000378:metabolism*
D001055:Apolipoproteins B; D001391:Azo Compounds; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D005372:Filipin; C011049:oil red O