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Can lipoprotein lipase be the culprit in cholesteryl ester accretion in smooth muscle cells in atheroma?

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      Abstract

      Bovine aortic smooth muscle cells and human skin fibroblasts were incubated with β-very low density lipoprotein (βVLDL) 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 βVLDL for up to 9 days and 60 min sodium heparin wash at 4°C to remove extracellular surface bound lipoprotein, cellular cholesterol increase was 2 μg in controls and in the presence of lipoprotein lipase (LPL) it was tenfold higher. Addition of [3H]cholesteryl ester labeled βVLDL 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 βVLDL and [3H]oleate induced no further increase in [3H]cholesteryl oleate. We propose that following LPL-mediated binding of βVLDL 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.

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