Abstract
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 dose- and time- dependent manner in human monocytic THP-1 cells, and the increase can be abolished by MAPK and NFκB pathway inhibitors. Lp-PLA2 inhibitor, 1-linoleoyl glycerol attenuates the inflammation induced by apo CIII. In turn, exogenous Lp-PLA2 expression upregulates apo CIII and the upregulation can be inhibited by 1-linoleoyl glycerol in HepG2 cells. Moreover, plasma Lp-PLA2 level is correlated with apo CIII expression in pig liver. In vivo, Lp-PLA2 expression in monocytes and its activity in serum were significantly increased in human apo CIII transgenic porcine models compared with wild-type pigs. Our results suggest that Lp-PLA2 and apo CIII expression level is correlated with each other in vitro and in vivo.
Highlights
Atherosclerosis is a chronic inflammatory disease that is associated with hypertriglyceridemia, hypercholesterolemia and vascular cell dysfunction
Effects of apo CIII on Lipoprotein-associated phospholipase A2 (Lp-PLA2) gene expression Lp-PLA2, as an independent biomarker and regulator of atherosclerosis, the level may be regulated by lipid associated
These results suggest that Lp-PLA2 at least partially mediates the effects of apo CIII on TNF-a, IL-6 and MCP-1 release in monocytic THP-1 cells
Summary
Atherosclerosis is a chronic inflammatory disease that is associated with hypertriglyceridemia, hypercholesterolemia and vascular cell dysfunction. RESULTS AND DISCUSSION Effects of apo CIII on Lp-PLA2 gene expression Lp-PLA2, as an independent biomarker and regulator of atherosclerosis, the level may be regulated by lipid associated To investigate the effect of apo CIII on Lp-PLA2 expression level, we treated human monocytic THP-1 cells with apo CIII.
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