title: 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.
abstract: Oxidized low-density lipoprotein (oxLDL) can bind to β2-glycoprotein I (β2GPI) 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, β2GPI, oxLDL, CRP/oxLDL, oxLDL/β2GPI or CRP/oxLDL/β2GPI. The results revealed the formation of foam cells in the oxLDL, CRP/oxLDL, oxLDL/β2GPI as well as CRP/oxLDL/β2GPI 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)‑1β, IL‑6 and tumor necrosis factor‑α were elevated in the CRP/oxLDL and CRP/oxLDL/β2GPI groups (P>0.05 vs. oxLDL), and obvious effects on p38/mitogen‑activated 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/βG2P1 complexes may induce lipid accumulation and inflammation in macrophages via the p38/MAPK and NF‑κB 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.
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Jie
authors: J
authors: Wang
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Mei-Jun
authors: MJ
authors: Feng
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Rui
authors: R
authors: Zhang
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: De-Min
authors: DM
authors: Yu
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Sai-Jun
authors: SJ
authors: Zhou
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Rui
authors: R
authors: Chen
authors: 2011 Collaborative Innovation Center of Tianjin For Medical Epigenetics, The Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Pei
authors: P
authors: Yu
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology*; D002784:Cholesterol / Q000032:analysis / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D008055:Lipids / Q000032:analysis / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D008055:Lipids; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D002784:Cholesterol; D020928:Mitogen-Activated Protein Kinases