• Atherosclerosis · May 2016

    Apolipoprotein A-1 binding protein promotes macrophage cholesterol efflux by facilitating apolipoprotein A-1 binding to ABCA1 and preventing ABCA1 degradation.

    • Min Zhang, Liang Li, Wei Xie, Jian-Feng Wu, Feng Yao, Yu-Lin Tan, Xiao-Dan Xia, Xiao-Yan Liu, Dan Liu, Gang Lan, Meng-Ya Zeng, Duo Gong, Hai-Peng Cheng, Chong Huang, Zhen-Wang Zhao, Xi-Long Zheng, and Chao-Ke Tang.
    • Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
    • Atherosclerosis. 2016 May 1; 248: 149-59.

    RationalePrevious studies have shown that apolipoprotein-1 (apoA-1) binding protein (AIBP) is highly associated with the regulation of apoA-1 metabolism, suggesting its role in the treatment of atherosclerosis. However, how AIBP regulates foam cell formation remains largely unexplored.ObjectiveTo investigate the mechanisms underlying AIBP inhibition of foam cell formation from macrophages.Methods And ResultsTHP-1-derived macrophages were incubated without or with apoA-1 and AIBP, followed by assessing the formation of foam cells and the potential mechanisms. Our results showed that AIBP and apoA-1 enhanced cholesterol efflux, altered the levels of cellular free cholesterol and cholesterol ester and prevented lipid accumulation so as to reduce the formation of foam cells. Meanwhile, lack of AIBP 115-123 amino acids resulted in the loss of AIBP binding to apoA-1. Moreover, our chemiluminescent analysis showed that AIBP promoted biotin-labeled apoA-1 binding to macrophages. Besides with AIBP, more apoA-1 bound to ABCA1, a key transporter responsible for cholesterol efflux to apoA-1, as indicated by our co-immunoprecipitation assay. Our results also showed that AIBP did not regulate ABCA1 mRNA expression, but stabilized its protein from CSN2-mediated degradation.ConclusionsAIBP promotes apoA-1 binding to ABCA1 on the cell membrane of macrophages and prevents ABCA1 protein from CSN2-mediated degradation so as to prevent foam cell formation. AIBP 115-123 amino acids is at least partially responsible for its binding to apoA-1.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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