C-reactive protein/oxidized low density lipoprotein/β2-glycoprotein I complexes induce lipid accumulation and inflammatory reaction in macrophages via p38/mitogen-activated protein kinase and nuclear factor-κB signaling pathways

Oxidized low-density lipoprotein (oxLDL) can bind to 2-glycoprotein I (2GPI) and C-reactive protein (CRP) to form stable complexes, which exert certain effects in diabetic cardiovascular disease. A previous study by our group has confirmed that the resulting complexes promote atherosclerosis in diabetic BALB/c mice. The present study was designed to investigate the effects and potential mechanisms of oxLDL complexes on lipid accumulation and inflammatory reactions in RAW264.7 macrophages cultured in a hyperglycemic environment. Cultured cells were divided into seven groups, which were treated with phosphate-buffered saline (control), CRP, 2GPI, oxLDL, CRP/oxLDL, oxLDL/2GPI or CRP/oxLDL/2GPI. The results revealed the formation of foam cells in the oxLDL, CRP/oxLDL, oxLDL/2GPI as well as CRP/oxLDL/2GPI groups. Compared with oxLDL, the three complexes induced less lipid accumulation (P<0.05) through inhibiting the expression of CD36 mRNA and promoting the expression of and ABCG1 mRNA (P<0.05 vs. oxLDL). Furthermore, the levels of inflammatory factors interleukin (IL)-1, IL-6 and tumor necrosis factor- were elevated in the CRP/oxLDL and CRP/oxLDL/2GPI groups (P>0.05 vs. oxLDL), and obvious effects on p38/mitogen-activated protein kinase and nuclear factor (NF)-B phosphorylation were also observed in these groups (P<0.05 vs. oxLDL). These results suggested that CRP/oxLDL/G2P1 complexes may induce lipid accumulation and inflammation in macrophages via the p38/MAPK and NF-B signaling pathways. However, some differences were observed between the complexes, which may be attributed to the property of each constituent; therefore, further studies are required.