PAF-acether decreases low density lipoprotein degradation and alters lipid metabolism in cultured human fibroblasts

A 24 h pretreatment of human cultured fibroblasts with PAF-acether (PAF) induced a decrease in LDL degradation and a correlative accumulation of undegraded LDL. LDL binding was not significantly affected. Sterol and triacylglycerol synthesis from sodium acetate was enhanced whereas phospholipid synthesis decreased. Oleic acid incorporation into cholesteryl ester was markedly inhibited, whereas incorporation into triacylglycerols was increased. A decrease in the percentage of phosphatidylcholine and an increase in the percentage of phosphatidylethanolamine were found using sodium [32P]orthophosphate as precursor. These effects of PAF on LDL and lipid metabolism could be related to perturbations in membrane structure characteristics, leading to a delay in LDL delivery to lysosomes, and to modification of the activity of some key enzymes of lipid metabolism.