C­reactive protein/oxidized low density lipoprotein/ß2­glycoprotein i complexes induce lipid accumulation and inflammatory reaction in macrophages via p38/mitogen­activated protein kinase and nuclear factor­κB signaling pathways.

Oxidized low-density lipoprotein (oxLDL) can bind to ß2-glycoprotein I (ß2GPI) 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 phosphate­buffered saline (control), CRP, ß2GPI, oxLDL, CRP/oxLDL, oxLDL/ß2GPI or CRP/oxLDL/ß2GPI. The results revealed the formation of foam cells in the oxLDL, CRP/oxLDL, oxLDL/ß2GPI as well as CRP/oxLDL/ß2GPI 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)­1ß, IL­6 and tumor necrosis factor­α were elevated in the CRP/oxLDL and CRP/oxLDL/ß2GPI groups (P>0.05 vs. oxLDL), and obvious effects on p38/mitogen­activated protein kinase and nuclear factor (NF)­κB phosphorylation were also observed in these groups (P<0.05 vs. oxLDL). These results suggested that CRP/oxLDL/ßG2P1 complexes may induce lipid accumulation and inflammation in macrophages via the p38/MAPK and NF­κB 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.