Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasorelaxation

We have recently found that remnant lipoproteins (RLPs) and their lipid fra ctions impair endothelium-dependent vasorelaxation (EDR). This study was ai med at clarifying mechanisms responsible for RLP-induced endothelial dysfun ction in isolated rabbit aortas. RLPs were isolated from plasma in hyperlip idemic subjects by use of the immunoaffinity gel mixture of anti-ApoA1 and anti-ApoB100 monoclonal antibodies and ultracentrifugation. Organ chamber e xperiments showed that EDR impairment was restored by addition of reduced g lutathione (GSH) or N-acetylcysteine, antioxidants, into the incubation buf fer containing isolated rabbit aortas and RLPs (0175 mg of triglyceride/mL) . Furthermore, the incubation of isolated human. red blood cells (RBCs) wit h RLP and its lipids converted the normal shape of RBCs to echinocytes, but coincubation with antioxidants suppressed the RTB-induced RBC transformati on, suggesting that they exerted oxidative damage on RBC surface membranes. Studies with HPLC and the postcolumn chemiluminescence method showed that RLPs contain a substantial amount of phosphatidylcholine hydroperoxides. Pe roxidized phosphatidylcholine also impaired EDR and bad echinocytogenic act ion, both of which were suppressed by N-acetylcysteine. RLPs isolated from the plasma of patients under treatment with alpha-tocopherol, an antioxidan t, had a lower level of phosphatidylcholine hydroperoxides (15% of the amou nt in nontreated patients), which was associated with a lack of the inhibit ory action on EDR and with lesser effect on RBC transformation. Oxidative d amage caused by lipid components in RLPs, especially peroxidized phospholip ids, deteriorates cell surface membrane and may be at least partly responsi ble for RLP-induced impairment of EDR.