Can lipoprotein lipase be the culprit in cholesteryl ester accretion in smooth muscle cells in atheroma?
Bovine aortic smooth muscle cells and human skin fibroblasts were incubated with beta-very low density lipoprotein (beta VLDL) isolated from cholesterol-fed rabbits and labeled with [3H]cholesteryl oleate. Addition of lipoprotein lipase resulted in a 3.2-4.8-fold increase in cell associated radioactivity of which 45-61% was in free cholesterol, i.e., derived after intracellular hydrolysis. After exposure of smooth muscle cells to beta VLDL for up to 9 days and 60 min sodium heparin wash at 4 degrees C to remove extracellular surface bound lipoprotein, cellular cholesterol increase was 2 micrograms in controls and in the presence of lipoprotein lipase (LPL) it was tenfold higher. Addition of [3H]cholesteryl ester labeled beta VLDL during the last 48 h of incubation showed that 30-40% of total cellular label was in free cholesterol. This value represents the minimal cellular uptake of the added lipoprotein cholesteryl ester. Addition of recombinant apolipoprotein (apo) E to smooth muscle cells incubated with beta VLDL and [3H]oleate induced no further increase in [3H]cholesteryl oleate. We propose that following LPL-mediated binding of beta VLDL to heparan sulphate, this complex either undergoes endocytosis, or translocation of cholesteryl ester into the smooth muscle cells (SMC) occurs without endocytosis of the entire particle. The present results indicate that in the aortic wall macrophage-derived lipoprotein lipase could play a role in cholesteryl ester accretion in smooth muscle cells during atherogenesis.
Stein
O
O
Department of Experimental Medicine and Cancer Research, Hadassah University Hospital, Jerusalem, Israel.
Ben-Naim
M
M
Dabach
Y
Y
Hollander
G
G
Halperin
G
G
Stein
Y
Y
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits
D002788:Cholesterol Esters; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase