Apolipoprotein B-100 peptide 210 antibody inhibits atherosclerosis by regulation of macrophages that phagocytize oxidized lipid

American Journal of Translational Research

Bingxin Cao¹  Zhuanglin Zeng² 

[1] Department of Interventional Radiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, Hubei, China;Laboratory of Cardiovascular Immunology, Key Laboratory of Molecular Targeted Therapies of The Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, Hubei, China

关键词: P210;    atherosclerosis;    cholesterol efflux;    inflammation;    macrophages;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Immunization with peptides derived from apolipoprotein B-100 (ApoB-100) has been shown to ameliorate atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. However, the exact mechanism underlying the therapeutic effects remains elusive. To shed light on this mechanism, we immunized ApoE-/- mice that were fed a Western diet with either malondialdehyde-modified ApoB-100 peptide 210 (P210) emulsified in Freund’s adjuvant or anti-malondialdehyde-modified P210 antibody (P210-Ab). Mice immunized with Freund’s adjuvant or bovine serum albumin served as controls. Macrophages were incubated in vitro with oxidized low-density lipoprotein (ox-LDL) or ox-LDL plus P210-Ab. Our results show that P210-Ab promoted cholesterol efflux, inhibited lipid accumulation in vitro, and reduced plasma levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. In addition, P210-Ab significantly attenuated macrophage infiltration and markedly improved the stability of atheromatous plaque. In conclusion, the anti-atherosclerotic effect of P210-Ab is related to its preferential inhibition of inflammation and reversion of cholesterol transportation by altering the pathway by which macrophages phagocytize ox-LDL.

【 授权许可】

CC BY-NC