The anti-inflammatory effect of paraoxonase 1 against oxidized lipids depends on its association with high density lipoproteins

Aim: The aims of this study were to investigate whether purified PON1 can reduce the pro-inflammatory effect of oxidized phospholipids and whether the effect depended on its association with HDL.

Main methods: Lipid peroxidation was induced by copper ions and was measured using the conjugated diene method. Lysophosphatidylcholine (lyso-PC) formation was measured by HPLC with evaporative light scattering detection (ELSD) and ICAM-1 expression on Ea.hy926 endothelial cells was analyzed by flow cytometry.

Key findings: Purified PON1 significantly inhibited copper-induced oxidation of LDL and HDL, causing a 60.5% and 77.7% decrease in conjugated diene formation, respectively. Incubating PON1 with oxLDL caused a significant increase in lyso-PC levels, while oxHDL caused a significant decrease. PON1 (12.5 to 50 μg/mL) had a pro-inflammatory effect in the presence of oxLDL, increasing ICAM-1 levels in Ea.hy926 cells by 33.0% and 40.6% (p<0.001) respectively, and had an anti-inflammatory effect in the presence of oxHDL, causing a 3-fold reduction in ICAM-1 levels. PON1 also caused a significant decrease in TNFα and purified lyso-PC-induced ICAM-1 expression. The results obtained with reconstituted HDL as well as LCAT and PAF-AH inhibitors suggested that the anti-inflammatory effect of PON1 against oxidized lipids is dependent on its association with HDL.

Significance: Our results clearly showed that PON1 is involved in the anti-inflammatory effect of HDL and that the effect appears to depend on its association with HDL.