OBJECTIVE: High-density lipoprotein (HDL) is believed to protect against development of atherosclerosis by inhibiting the accumulation of oxidized lipids in low-density lipoprotein (LDL). Paradoxically, HDL lipid is more susceptible to oxidation than LDL lipid. In the present study, we examined the effect of oxidized phospholipids on the uptake of HDL by macrophages. METHODS AND RESULTS: Oxidation of HDL increased formation of phosphatidylcholine core aldehydes that was paralleled by increased covalent binding of phospholipids to HDL protein from 0.96+/-0.44 to 8.5+/-1.76 phosphorus/HDL protein (mol/mol). Incubation of apolipoprotein AI with synthetically prepared phosphatidylcholine core aldehydes, 1-palmitoyl-2-[5-oxo]valeroyl-sn-glycero-3-phosphocholine or 1-palmitoyl-2-[9-oxo] nonanoyl-sn-glycero-3-phosphocholine, significantly increased the phosphorus:apolipoprotein AI ratio from 1.1+/-0.5 to 7.2+/-2.0 and from 0.9+/-0.6 to 8.5+/-0.8, respectively. The binding and uptake of phosphatidylcholine core aldehyde-apolipoprotein AI proteoliposomes, by THP-1 macrophages, was similar to that observed for oxidized HDL and oxidized LDL. CONCLUSION: We conclude that oxidation of HDL increased formation of phosphatidylcholine core aldehyde-apolipoprotein AI Schiff base adducts and enhanced uptake of oxidized HDL by THP-1 macrophages.
OBJECTIVE: High-density lipoprotein (HDL) is believed to protect against development of atherosclerosis by inhibiting the accumulation of oxidized lipids in low-density lipoprotein (LDL). Paradoxically, HDL lipid is more susceptible to oxidation than LDL lipid. In the present study, we examined the effect of oxidized phospholipids on the uptake of HDL by macrophages. METHODS AND RESULTS: Oxidation of HDL increased formation of phosphatidylcholine core aldehydes that was paralleled by increased covalent binding of phospholipids to HDL protein from 0.96+/-0.44 to 8.5+/-1.76 phosphorus/HDL protein (mol/mol). Incubation of apolipoprotein AI with synthetically prepared phosphatidylcholine core aldehydes, 1-palmitoyl-2-[5-oxo]valeroyl-sn-glycero-3-phosphocholine or 1-palmitoyl-2-[9-oxo] nonanoyl-sn-glycero-3-phosphocholine, significantly increased the phosphorus:apolipoprotein AI ratio from 1.1+/-0.5 to 7.2+/-2.0 and from 0.9+/-0.6 to 8.5+/-0.8, respectively. The binding and uptake of phosphatidylcholine core aldehyde-apolipoprotein AI proteoliposomes, by THP-1 macrophages, was similar to that observed for oxidized HDL and oxidized LDL. CONCLUSION: We conclude that oxidation of HDL increased formation of phosphatidylcholine core aldehyde-apolipoprotein AI Schiff base adducts and enhanced uptake of oxidized HDL by THP-1 macrophages.