Formation of apolipoprotein AI-phosphatidylcholine core aldehyde Schiff base adducts promotes uptake 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.


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.


CONCLUSIONS
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.
Ahmed
Zakaria
Z
Department of Pathology and Laboratory Medicine, University of Louisville Medical Center, Louisville, KY 40202, USA.
Ravandi
Amir
A
Maguire
Graham F
GF
Kuksis
Arnis
A
Connelly
Philip W
PW
D000447:Aldehydes / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002460:Cell Line; D008076:Cholesterol, HDL / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism*; D012545:Schiff Bases / Q000378:metabolism
D000447:Aldehydes; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D018736:DNA Adducts; D008081:Liposomes; D010713:Phosphatidylcholines; D012545:Schiff Bases