Independent regulation of cholesterol incorporation into free apolipoprotein-mediated cellular lipid efflux in rat vascular smooth muscle cells.
Cholesterol was poorly available to free apolipoprotein (apo)A-I-mediated cellular lipid efflux from cholesterol-loaded rat vascular smooth muscle cells generating cholesterol-poorer pre-beta-HDL particles than those generated from macrophages by the same reaction (Li, Q., Komaba, A., and Yokoyama, S. (1993) Biochemistry 32, 4597-4603). The factors known to induce transformation of the smooth muscle cells into a macrophage-like stage were used in order to modulate this reaction, such as human platelet-derived growth factor, macrophage colony-stimulating factor, and phorbol 12-myristate-13-acetate (PMA). When the cells were stimulated by PMA following the pretreatment with platelet-derived growth factor plus macrophage colony-stimulating factor, cholesterol efflux mediated by free apoA-I increased 3-fold without changing phospholipid efflux, resulting in generation of pre-beta-HDL particles more rich in cholesterol. This treatment had only a little or no effect on apparent cellular cholesterol efflux to HDL or lipid microemulsion, respectively. Overall cellular free cholesterol pool size was unaffected by the treatment, and probing by extracellular cholesterol oxidase did not detect gross change in the cellular surface cholesterol. This specific enrichment of cholesterol in the apoA-I-mediated cellular lipid efflux was reversed by protein kinase C inhibitors. Measurement of intracellular cholesterol esterification suggested that PMA induced translocation of intracellular cholesterol to a specific pool for apoA-I-mediated efflux, and a protein kinase C inhibitor reversed this effect.
Li
Q
Q
Department of Medicine, University of Alberta, Edmonton, Canada.
Yokoyama
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D004655:Emulsions; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016632:Apolipoprotein A-I; D008078:Cholesterol, LDL; D004655:Emulsions; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D010982:Platelet-Derived Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D013755:Tetradecanoylphorbol Acetate