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

作者：Zeng, Zhuanglin; Cao, Bingxin; Guo, Xiaopeng; Li, Weijuan; Li, Songhai; Chen, Juan; Zhou, Wenping; Zheng, Chuansheng^*; Wei, Yumiao^*

来源：American Journal of Translational Research, 2018, 10(6): 1817-1828.

• P210
• atherosclerosis
• cholesterol efflux
• inflammation
• macrophages

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-alpha), 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 (alpha) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) 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.

• 出版日期2018
• 单位华中科技大学