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  • Title: Oxidized low-density lipoprotein (LDL) enhances thromboxane A(2) synthesis by platelets, but lysolecithin as a product of LDL oxidation has an inhibitory effect.
    Author: Mahfouz MM, Kummerow FA.
    Journal: Prostaglandins Other Lipid Mediat; 2000 Jul; 62(2):183-200. PubMed ID: 10938412.
    Abstract:
    Oxidation of low-density lipoprotein (LDL) by copper sulfate led to a significant increase in lysophosphatidylcholine (lyso PC) at the expense of phosphatidylcholine. Incubation of different concentrations of oxidized LDL (oxLDL) (32-650 microg protein/ml) with platelets for 1 h at 37 degrees C increased lyso PC content. The increase was dependent on oxLDL concentration. Incubation of platelets with various concentrations of lyso PC in solution for 5 or 15 min showed that lyso PC percentage was increased in the platelet membrane and the increase was dose dependent. Platelets incubated with various concentrations of lyso PC (2-100 microM) for 5 or 15 min and then triggered with thrombin also showed a significant decrease of thromboxane A(2) (TXA(2)) release as lyso PC concentration reached 10 microM or 6 microM, respectively. The decrease of TXA(2) release was more significant as lyso PC concentration was increased. The present study showed that this inhibition of TXA(2) release by lyso PC was due to 1) inhibition of phospholipase A(2) and the decrease of free arachidonic acid liberation from platelet phospholipid and 2) inhibition of cyclooxygenase. These inhibitory effects of lyso PC were discussed in relation to its effect on membrane fluidity. Lyso PC at concentrations of 30, 50, and 100 microM caused a sudden drop in TXA(2) release and a sudden increase of lactic dehydrogenase loss from the platelets due to their lysis and inhibition of cyclooxygenase enzyme. The present study shows that oxLDL contains high levels of lyso PC that are transferable to the platelets and can weaken their responsiveness to thrombin and decrease TXA(2) release. In our previous study, we found that oxLDL also contained high levels of oxysterols and thiobarbituric acid reactive substances (TBARS), which enhanced platelet reactivity to thrombin and increased TXA(2) release. We conclude that the net effect of oxLDL on platelets will depend on its degree of oxidation and the ratio between oxysterols plus TBARS/lyso PC. Variations in this ratio may explain some of the contradictions cited in the literature concerning the effect of oxLDL on platelet activation.
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