EFFECT OF RETINOIDS ON LDL METABOLISM BY MACROPHAGES

Hyperlipidemia can occur during retinoid treatment. Macrophages are in volved in lipid metabolism and in the pathomechanism of atherosclerosi s. The aim of the study was to determine whether retinoids have any ef fect on low density lipoprotein (LDL) metabolism by macrophages throug h their specific or scavenger LDL receptors. Both receptor pathways ca n be investigated using a 72 h culture of monocytes. In the case of th e specific LDL receptor, I-125-LDL binding, degradation and cholestero l synthesis (C-14 acetate incorporation), in the case of the scavenger LDL receptor, I-125-acetylated LDL (I-125-acLDL) binding, degradation , and apolipoprotein E secretion (laser nephelometry) were studied on a 72 h, monocyte-derived macrophage culture obtained from 12 healthy v olunteers and 5 isotretinoin-treated patients. Retinoic acids (RAs) (a ll-trans-retinoic acid and 13-cis-retinoic acid) were added in vitro i n 1 mu M, to the cultures from healthy volunteers and compared with cu ltures from retinoid-treated patients. There was no significant differ ence in terms of I-125-LDL and I-125-acLDL binding, degradation and th e cholesterol synthesis inhibition effect of LDL in RAs-treated cultur es versus retinoid-treated patients and their respective controls. Apo E secretion in monolayers derived from healthy volunteers in the prese nce of retinoic acids and from retinoid-treated patients were decrease d as compared to the controls. Reduced apoE secretion by macrophages m ay be involved in retinoid-induced hypercholesterolemia.