Cholesteryl ester efflux from extracellular and cellular elements of the arterial wall. Model systems in culture with cholesteryl linoleyl ether.
Cholesteryl ester (CE) accretion in human atheroma is a slow process during which lipoproteins infiltrate the arterial extracellular space and then gain entry into the cellular components. The present aim was to simulate this process in model systems in culture to learn whether cholesteryl ester transfer protein (CETP) may promote CE efflux at different stages of atheroma formation. To simulate CE efflux from arterial interstitium, cationized LDL labeled with 3H-cholesteryl linoleyl ether (3H-CLE) was added to fixed aortic smooth muscle cells (SMC) or to extracellular matrix. To study efflux of 3H-CLE taken up by cells via receptor-mediated endocytosis of LDL, the SMC cultures were fixed and permeabilized prior to the determination of CE efflux. The cellular model included macrophages, which had ingested acetylated LDL labeled with 3H-CLE. Efflux of 3H-CLE and 14C-CE was studied during postincubation of the labeled cultures with human lipoprotein deficient serum (LPDS) or partially purified CETP. As controls, we used SMC cultures incubated with albumin. In all systems, a 3- to 12-fold increase of 3H-CLE or 14C-CE efflux was found in the postincubation medium containing human LPDS or partially purified CETP when compared to controls. Permeabilization of the cells with saponin enhanced cellular 3H-CLE and 14C-CE efflux in the presence of human LPDS. The findings indicate that CETP may promote CE efflux from aortic interstitium or disintegrating cells. We propose that CETP may play an important role in aortic CE homeostasis under physiological and pathological conditions.
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism; D006023:Glycoproteins; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008081:Liposomes; C027575:cholesteryl linoleyl ether; D002784:Cholesterol