Effect of retinoids on LDL metabolism by macrophages

Hyperlipidemia can occur during retinoid treatment. Macrophages are involved in lipid metabolism and in the pathomechanism of atherosclerosis. The aim of the study was to determine whether retinoids have any effect on low density lipoprotein (LDL) metabolism by macrophages through their specific or scavenger LDL receptors. Both receptor pathways can be investigated using a 72 h culture of monocytes. In the case of the specific LDL receptor, I-125-LDL binding, degradation and cholesterol 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 volunteers and 5 isotretinoin-treated patients. Retinoic acids (RAs) (all-trans-retinoic acid and 13-cis-retinoic acid) were added in vitro in 1 mu M, to the cultures from healthy volunteers and compared with cultures from retinoid-treated patients. There was no significant difference in terms of I-125-LDL and I-125-acLDL binding, degradation and the cholesterol synthesis inhibition effect of LDL in RAs-treated cultures versus retinoid-treated patients and their respective controls. ApoE secretion in monolayers derived from healthy volunteers in the presence of retinoic acids and from retinoid-treated patients were decreased as compared to the controls. Reduced apoE secretion by macrophages may be involved in retinoid-induced hypercholesterolemia.