| ω3-PUFAs have a protective effect against cardiovascular events. A number ofclinical studies have demonstrated that the consumption of ω3-PUFAs improveslipoprotein metabolism, cardiac function, endothelial function, vascular reactivity andinflammatory responses in cardiovascular disease (CVD). Lp-PLA2, also known asplatelet-activating factor (PAFAH), is a noval specific marker of vascularinflammation and atherosclerosis. Basic research and clinical experiments haveindicated that there is a close relationship between Lp-PLA2and cardiovascularevents.In recent years, studies have found that ω3-PUFAs improve the activity of Lp-PLA2inpatients with cardiovascular disease. However, effects of ω3-PUFAs on Lp-PLA2expression and its mechanism remain to be further studied. Here, we investigated theeffects of ω3-PUFAs on Lp-PLA2expression in vitro and in vivo, together with themechanisms involved.To determine the roles of ω3-PUFAs in Lp-PLA2in macrophages,THP-1-derived macrophages were supplemented with or without ω3-PUFAs24hours. Western blot and immunofluorescence analysis of Lp-PLA2expression foundthat ω3-PUFAs suppress the Lp-PLA2expression significantly (P <0.001), whereasω6-PUFAs have the opposite effect. In addition, TNF-α-primed THP-1-derivedmacrophages were supplemented with or without ω3-PUFAs. Western blot analysis ofLp-PLA2, TNF-α, p38MAPK, p-p38MAPK, p65NF-κB and p-p65NF-κB foundthat ω3-PUFAs mediated-inhibition of Lp-PLA2includes the inactivation of theNF-κB and MAPK signalling pathways.Then, a chronic inflammation mouse model was established with HFD andcasein hypodermic injection, in which Lp-PLA2expression in peripheral blood mononuclear cells (PBMCs) and arteries were increased. With the supplement ofω3-PUFAs, Lp-PLA2were suppressed. Elisa analysis of serum inflammatory factorsof mouse model found that ω3-PUFAs suppress the level of inflammatory factors.Immunofluorescence staining revealed that macrophages with the localization ofLp-PLA2were accumulated in the arteries of the HC group, Lp-PLA2expression andmacrophage accumulation were reduced in the HC with ω3-PUFAs group.Additionally, inhibition of Lp-PLA2transcription in PBMCs was also observed in theω3-PUFA-enriched hFat-1transgenic swine.This study revealed effects of ω3-PUFAs on Lp-PLA2and its mechanism. Ourresults demonstrated that the protective effects of ω3-PUFAs against cardiovascularevents may be related to the suppression of Lp-PLA2levels. |
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