Dual effect of lovastatin and simvastatin on LDL-macrophage interaction.
نویسندگان
چکیده
Lovastatin and simvastatin which are very potent cellular cholesterol biosynthesis inhibitors, significantly affect the plasma lipoprotein concentration. After incubation of plasma with 14C-labelled compounds, radioactivity was found in all lipoprotein fractions but mainly (40%) in high density lipoprotein (HDL), and in the lipoprotein-deficient plasma fraction (20-30%). Drug-treated lipoproteins showed reduced electrophoretic mobility on cellulose acetate in comparison with control lipoproteins. The lovastatin-treated low density lipoprotein (LDL) displayed 28% increased fluidity in comparison with control LDL. The immunoreactivity of drug-treated LDL with monoclonal antibody directed towards the LDL receptor binding domains (B1B6) was significantly less than that of control LDL, suggesting reduced binding to the LDL receptor. When drug-treated LDL was incubated with J-774 A.1 macrophage-like cell line, its binding (at 4 degrees C) was 28% less than that of control LDL, whereas a substantial increase in the cellular cholesterol esterification rate (by 83% with lovastatin and by 67% with simvastatin) was noted. Similarly, the degradation of lovastatin and simvastatin-treated LDL by macrophages was 87-89% greater than that of control LDL. The "apparent Vmax" for the macrophage degradation of lovastatin-treated LDL was 70% greater than that for control LDL. Thus, both drugs may have a dual effect on the macrophage uptake of LDL; they may increase the number of LDL receptors on the cell surface, but they may also reduce the affinity of LDL for its receptor, the former being the major effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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عنوان ژورنال:
- European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies
دوره 29 10 شماره
صفحات -
تاریخ انتشار 1991