Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFkB pathways

Apolipoprotein CIII (apo CIII), a small glycoprotein that binds to the surfaces of certain lipoproteins, is associated with inflammatory and atherogenic responses in vascular cells. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory biomarker and potential therapeutic target for cardiovascular disease (CVD). Here, we report that apo CIII increases Lp-PLA2 mRNA and protein levels in doseand timedependent manner in human monocytic THP-1 cells, and the increase can be abolished by MAPK and NFkB pathway inhibitors. Lp-PLA2 inhibitor, 1-linoleoyl glycerol attenuates the inflammation inducedbyapoCIII. In turn, exogenous LpPLA2 expression upregulates apo CIII and the upregulation can be inhibited by 1-linoleoyl glycerol in HepG2 cells. Moreover, plasma LpPLA2 level is correlated with apoCIII expression in pig liver. In vivo, LpPLA2 expression in monocytes and its activity in serum were significantly increased in human apo CIII transgenic porcine models comparedwithwild-typepigs.Our resultssuggest thatLp-PLA2andapo CIII expression level is correlated with each other in vitro and in vivo.