Lipoprotein-like phospholipid particles inhibit the smooth muscle cell cytotoxicity of lysophosphatidylcholine and platelet-activating factor.
Oxidation of LDL is associated with degradation of phosphatidylcholine into platelet-activating factor (PAF)-like phospholipids and lysophosphatidylcholine (LPC). Exposure of cultured human smooth muscle cells to PAF and LPC in a concentration of 25 micromol/L was found to result in complete cell death, as assessed by the MTT cytotoxicity assay and cell counting. Addition of 50 microg/mL apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles completely inhibited this cytotoxicity. Phospholipid complexes alone were almost as effective, whereas free apolipoprotein A-I(Milano) and albumin were without effect, suggesting that the effect was phospholipid dependent. Experiments using [14C]LPC demonstrated that apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles effectively bind LPC. The results show that HDL-like phospholipid particles effectively inhibit the toxic effect of phospholipids and other lipid-soluble factors. The ability of HDL to inhibit the proinflammatory and toxic effects of phospholipids generated during oxidation of LDL may be responsible for part of the antiatherogenic properties of HDL.
Nilsson
J
J
King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Dahlgren
B
B
Ares
M
M
Westman
J
J
Hultgårdh Nilsson
A
A
Cercek
B
B
Shah
P K
PK
D016632:Apolipoprotein A-I / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002250:Carbon Radioisotopes; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003603:Cytotoxins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D016632:Apolipoprotein A-I; D002250:Carbon Radioisotopes; D003603:Cytotoxins; D006888:Hydroxycholesterols; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D010972:Platelet Activating Factor; C080631:apolipoprotein A-I Milano; C011724:cholest-5-en-3 beta,7 alpha-diol; C007997:25-hydroxycholesterol