| Nitrated fatty acids are involved in multiple signaling pathways, acting asanti-inflammatory signaling mediators and protecting the vasculature.Lipoprotein-associated phospholipase A2(Lp-PLA2) is well known as acardiovascular risk biomarker, which is a potential therapeutic target. Here, we testedthe hypothesis that nitro-oleic acid (OA-NO2) affects the expression and function ofLp-PLA2.We determined the expression of Lp-PLA2in THP-1cells after stimulation with0.05μM PMA when monocytes were transformed into macrophages; the cells werepretreated with OA-NO2for1h before PMA activation. The results showed thatOA-NO2down-regulated the expression of Lp-PLA2in a time-and dose-dependentmanner, while native OA had no such effect. Furthermore, it was previously foundthat OA-NO2can repress Lp-PLA2expression in the macrophages of apoCIII-transgenic pigs (apo CIII TG), which exhibit higher Lp-PLA2expression andactivity than the wild-type (WT) pigs. OA-NO2inhibits cell proliferation indose-dependent manner, while OA have no effect on the cell proliferation. OA-NO2down-regulates Lp-PLA2via inhibiting the phosphorylation of both p42/p44mitogen-activated protein kinase (MAPK), and it also could reduce Lp-PLA2expression via the nuclear factor κB (NFκB) pathway including the inhibition ofphosphorylation of NFκB and activity of NFκB/DNA binding. However, as NO donorand potent ligand of PPARγ, OA-NO2inhibits Lp-PLA2expression in macrophages,independent of nitric oxide formation and PPARγ-activation. As an anti-inflammatorysignaling mediator, OA-NO2not only suppresses the release of cytokines but alsoincreases the activity of SOD. In contrast, Lp-PLA2promotes the release of cytokinesand decreases the activity of SOD. Thus, OA-NO2down-regulates Lp-PLA2 expression, associated with the reduction of pro-inflammatory cytokines and reactiveoxygen species (ROS).OA-NO2may exert a vascular-protective effect partially via Lp-PLA2inhibition. |
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