Key result
ApoC-III almost completely inhibits apoE-mediated cholesterol uptake in HepG2 cells despite sufficient apoE binding.
Why the study?
Apolipoprotein C-III decreases apoE-mediated uptake of lipoprotein remnants by the liver, but the mechanisms involving cholesterol-containing lipoprotein particles are not fully understood.
ApoC-III attenuates apoE-mediated cellular uptake of lipoprotein remnants, providing mechanistic insight into its association with hypertriglyceridemia and coronary heart disease risk.
Offers no immediate clinical implications; extends animal mechanistic insight into apoC-III but leaves open human translation.
Apolipoprotein C-III (apoC-III) decreases the apolipoprotein E (apoE)-mediated uptake of lipoprotein remnants by the liver, and a high plasma concentration of apoC-III in VLDL is associated with hypertriglyceridemia and the risk of coronary heart disease. In this study, we prepared lipid emulsions containing triolein, phosphatidylcholine and cholesterol as model particles of lipoproteins, and examined the roles of apoC-III in apoE-mediated uptake of emulsions by HepG2 cells. Cholesterol in emulsion particles enhanced the apoE-mediated uptake via heparan sulfate proteoglycan and LDL receptor-related protein pathways. The amount of apoE bound to emulsion particles was increased by the presence of cholesterol at the particle surface, whereas cholesterol had no effect on the binding amount of apoC-III. Surface cholesterol alleviated the inhibitory effect of apoC-III on apoE incorporation into the emulsion surface. However, ApoC-III almost completely inhibited the apoE-mediated uptake of cholesterol-containing emulsions despite sufficient binding of apoE to emulsions. These findings suggest that apoC-III attenuates the binding of apoE to the lipoprotein surface and apoE-mediated cellular uptake of lipoprotein remnants. Furthermore, cholesterol may affect these functions of apoC-III and apoE involved in the clearance of lipoprotein remnants.
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Morita et al. (2010) studied this question. Apolipoprotein C-III was evaluated on apoE-mediated cellular uptake of cholesterol-containing lipid particles by HepG2 cells. Apolipoprotein C-III almost completely inhibited the apoE-mediated uptake of cholesterol-containing emulsions by HepG2 cells despite sufficient binding of apoE to the emulsions.
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