Effect of Differential Oxidation of LDL on Foam Cell Formation and Expression of MMP-9 and CD147 in PMA-Derived Macrophage Foam Cells

High plasma low-density lipoprotein (LDL) levels can trigger phagocytosis of macrophages to become foam cells that can initiate atherosclerosis progression. LDL undergoes stepwise oxidation to minimally modified LDL (mm-LDL) and fully oxidized LDL (ox-LDL). This study investigated the effect of LDL with different degrees of oxidation, including LDL, mm-LDL and ox-LDL, on foam cell formation and expression of MMP-9 and CD147 in macrophages. Phorbol 12-myristate 13-acetate-derived macrophages from U937 cells were used as the study model. Cells were co-cultivated with or without different types of LDL at various concentrations and times before characterization. The results revealed that LDL induced the strongest intracellular lipid response, with conversion of macrophages to foam cells. Upregulation of CD36, but not of LDL receptors, was observed on incubation with all types of LDL, suggesting its role in the endocytosis of the studied LDLs. Upregulation of MMP-9 in foam cells was observed both in cell lysates and in the secreted form after 48 h of cultivation. MMP-9 conversion from pro-form to active form was detected after 72 h of cultivation with all types of LDL, but most strongly with LDL and ox-LDL, and was correlated with the upregulation of membrane-bound CD147 (mCD147). In summary, this study indicates that different degrees of LDL oxidation induced different severities of foam cell formation, induction of MMP-9 and mCD147. HIGHLIGHTS Cell surface CD36 was upregulated on PMA-derived macrophages from U937 cells. LDL, mm-LDL and ox-LDL produced different extents of foam cell formation. LDL induced higher intracellular cholesterol concentrations than mm-LDL and ox-LDL. Upregulation of MMP-9 and mCD147 in macrophage foam cells was stronger by LDL than by ox-LDL. GRAPHICAL ABSTRACT