PMID- 24882274 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20140726 IS - 1879-2472 (Electronic) IS - 0049-3848 (Linking) VI - 134 IP - 2 DP - 2014 Aug TI - oxLDL/beta2GPI/anti-beta2GPI complex induced macrophage differentiation to foam cell involving TLR4/NF-kappa B signal transduction pathway. PG - 384-92 LID - S0049-3848(14)00282-5 [pii] LID - 10.1016/j.thromres.2014.05.017 [doi] AB - Macrophage-derived foam cell formation is a hallmark of atherosclerosis. It has been reported that oxidized low density lipoprotein (oxLDL) inducing formation of foam cells and expression of inflammatory molecules are partly mediated by toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappaB) pathway. However, whether oxLDL/beta2-glycoprotein I/anti-beta2-glycoprotein I (oxLDL/beta2GPI/anti-beta2GPI) complex enhanced formation of foam cells involving TLR4/NF-kappaB pathway or not has never been explored. In the current study, we focused on investigating the transformation of peritoneal macrophages from BALB/c mice into foam cells induced by the three complexes, and the involvement of TLR4 as well as its downstream signal molecule NF-kappaB. The results showed that treatment of macrophages with oxLDL/beta2GPI/anti-beta2GPI complex could markedly increase intracellular lipid loading and expression of TLR4, phosphorylated NF-kappaB p65 (p-NF-kappaB p65), monocyte chemoattractant protein-1 (MCP-1), as well as tissue factor (TF). The oxLDL and oxLDL/beta2GPI/anti-beta2GPI complex induced formation of foam cells and expression of p-NF-kappaB p65 were significantly reduced, while macrophages were pre-treated with TLR4 inhibitor TAK-242. Meanwhile, both TAK-242 and NF-kappaB inhibitor PDTC could remarkably inhibit oxLDL, oxLDL/beta2GPI/anti-beta2GPI complex, as well as LPS increased MCP-1 and TF levels. Nevertheless, beta2GPI/anti-beta2GPI complex-induced MCP-1 and TF mRNA expression were inhibited by TAK-242 rather than PDTC, although TF activity was significantly reduced by both of the inhibitors. In conclusion, our results indicate that oxLDL/beta2GPI/anti-beta2GPI complex could enhance the conversion of macrophages into foam cells and the process may be at least partly mediated by TLR4/NF-kappaB pathway, which may contribute to the accelerated development of atherosclerosis in APS. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Xu, Ya AU - Xu Y AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; The First Affiliated Hospital of Soochow University, Suzhou First People's Hospital. FAU - Kong, Xiangmin AU - Kong X AD - Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Zhou, Hong AU - Zhou H AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: hongzhou@ujs.edu.cn. FAU - Zhang, Xiaolei AU - Zhang X AD - Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Liu, Jingjing AU - Liu J AD - Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Yan, Jinchuan AU - Yan J AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: yanjinchuan@hotmail.com. FAU - Xie, Hongxiang AU - Xie H AD - Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Xie, Yachao AU - Xie Y AD - Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140520 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Chemokine CCL2) RN - 0 (Lipoproteins, LDL) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptor 4) RN - 0 (beta 2-Glycoprotein I) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Chemokine CCL2/immunology MH - Foam Cells/cytology/*immunology MH - Lipoproteins, LDL/*immunology MH - Macrophages, Peritoneal/cytology/*immunology MH - Mice MH - Mice, Inbred BALB C MH - NF-kappa B/*immunology MH - Signal Transduction MH - Toll-Like Receptor 4/*immunology MH - beta 2-Glycoprotein I/*immunology OTO - NOTNLM OT - MCP-1 OT - NF-kappaB OT - TF OT - TLR4 OT - foam cell OT - oxLDL/beta2GPI/anti-beta2GPI complex EDAT- 2014/06/03 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/06/03 06:00 PHST- 2013/12/30 00:00 [received] PHST- 2014/04/11 00:00 [revised] PHST- 2014/05/08 00:00 [accepted] PHST- 2014/06/03 06:00 [entrez] PHST- 2014/06/03 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - S0049-3848(14)00282-5 [pii] AID - 10.1016/j.thromres.2014.05.017 [doi] PST - ppublish SO - Thromb Res. 2014 Aug;134(2):384-92. doi: 10.1016/j.thromres.2014.05.017. Epub 2014 May 20.