Heparin inhibits the accumulation of re-esterified cholesterol in macrophages loaded with acetylated low-density lipoprotein.
Heparin enhances the endocytosis of low density lipoprotein (LDL) in macrophages via a formation of complex with LDL. The direct effect of heparin on the metabolism of cholesterol in macrophages has not been elucidated. We therefore evaluated the effects of heparin on the accumulation and reesterification of cholesterol in cultured macrophages. We used acetylated LDL (acetyl-LDL), which lacks an affinity for heparin. Rat peritoneal macrophages induced with thioglycollate were incubated with 100 micrograms of acetyl-LDL for 14 h. Heparin significantly inhibited the accumulation of total and esterified cholesterol but did not affect the binding of 125I-labeled acetyl-LDL to macrophages or its cellular degradation. Heparin at concentration above 5 micrograms/ml inhibited the incorporation of [3H]oleate into cholesteryl oleate in macrophages. Heparin significantly inhibited the acyl CoA:cholesterol acyl transferase (ACAT) activity of macrophages by 68%. Data suggest that heparin inhibits the accumulation and reesterification of cholesterol in macrophages loaded with acetyl-LDL. Heparin-like proteoglycans may thus protect the macrophages against the excessive accumulation of esterified cholesterol.
D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004951:Esterification; D005312:Fetal Blood; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D013864:Thioglycolates / Q000494:pharmacology
D002788:Cholesterol Esters; D003470:Culture Media; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D013864:Thioglycolates; C032629:acetyl-LDL; D019301:Oleic Acid; D006493:Heparin; D002785:Sterol O-Acyltransferase