LIPOPROTEIN-LIKE PHOSPHOLIPID PARTICLES INHIBIT THE SMOOTH-MUSCLE CELL CYTOTOXICITY OF LYSOPHOSPHATIDYCHOLINE AND PLATELET-ACTIVATING-FACTOR

Oxidation of LDL is associated with degradation of phosphatidylcholine into platelet-activating factor (PAF)-like phospholipids and lysophos phatidylcholine (LPC). Exposure of cultured human smooth muscle cells to PAF and LPC in a concentration of 25 mu mol/L was found to result i n complete cell death, as assessed by the MTT cytotoxicity assay and c ell counting. Addition of 50 mu g/mL apolipoprotein A-I- and apolipopr otein A-I-Milano-containing phospholipid particles completely inhibite d this cytotoxicity. Phospholipid complexes alone were almost as effec tive, whereas free apolipoprotein A-I-Milano and albumin were without effect, suggesting that the effect was phospholipid dependent. Experim ents using [C-14]LPC demonstrated that apolipoprotein A-I-and apolipop rotein A-I-Milano-containing phospholipid particles effectively bind L PC. The results show that HDL-like phospholipid particles effectively inhibit the toxic effect of phospholipids and other lipid-soluble fact ors. The ability of HDL to inhibit the proinflammatory and toxic effec ts of phospholipids generated during oxidation of LDL may be responsib le for part of the antiatherogenic properties of HDL.