551. Enhanced Atherosclerosis in TIPE2-Deficient Mice Is Associated with Increased Macrophage Responses to Oxidized Low-Density Lipoprotein.
- Author
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Yunwei Lou, Suxia Liu, Cheng Zhang, Guizhong Zhang, Jingjing Li, Mei Ni, Guipeng An, Mei Dong, Xiaoling Liu, Faliang Zhu, Wenqian Zhang, Fei Gao, Chen, Youhai H., and Yun Zhang
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ATHEROSCLEROSIS treatment , *LOW density lipoproteins , *BONE marrow transplantation , *IMMUNOREGULATION , *CELL culture , *JANUS kinases , *CELLULAR signal transduction , *MAMMALS ,ANIMAL models of atherosclerosis - Abstract
Atherosclerosis has been widely recognized as an inflammatory disease of the arterial wall in which macrophages play a major role. Yet, how macrophage-mediated pathology is regulated during atherosclerosis is poorly understood. TNF-a-induced protein 8-like 2 (TIPE2, also known as TNFAIP8L2) is highly expressed in resting macrophages and can negatively regulate inflammation through inhibiting immune receptor signaling. We report in this article that TIPE2 plays a crucial atheroprotective role likely by regulating macrophage responses to oxidized low-density lipoprotein (ox-LDL). TIPE2-deficient macrophages treated with ox- LDL produced more oxidative stress and proinflammatory cytokines, and exhibited heightened activation of the JNK, NF-κB, and p38 signaling pathways. As a consequence, TIPE2 deficiency in bone marrow-derived cells exacerbated atherosclerosis development in Ldlr-/- mice fed a high-fat diet. Importantly, ox-LDL markedly downregulated TIPE2 mRNA and protein levels in macrophages, suggesting that ox-LDL mediates atherosclerosis by TIPE2 inhibition. These results indicate that TIPE2 is a new inhibitor of atherosclerosis and a potential drug target for treating the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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