摘要：
Objectives: ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. This study was to determine the effects and potential mechanisms of Chlamydia pneumoniae (C. pneumoniae) on ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells. Methods and results: C. pneumoniae significantly decreased the expression of ABCA1 and reduced cholesterol efflux. Furthermore, we found that C. pneumoniae suppressed ABCA1 expression via upregulation of miR-33s. The inhibition of C. pneumoniae-induced NF-kappa B activation decreased miR-33s expression and enhanced ABCA1 expression. In addition, C. pneumoniae increased Toll-like receptor 2 (TLR2) expressions, inhibition of which by siRNA could also block NF-kappa B activation and miR-33s expression, and promot the expression of ABCA1. Conclusion: Taken together, these results reveal that C. pneumoniae may negatively regulate ABCA1 expression via TLR2-NF-kappa B and miR-33 pathways in THP-1 macrophage-derived foam cells, which may provide new insights for understanding the effects of C. pneumoniae on the pathogenesis of atherosclerosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
作者机构：
[Zhong-Cheng Mo; Ji Xiao; Zhi-feng Long; Guang-hui Yi; Feng Yao; Yu-lin Tan; Min Zhang; Guo-jun Zhao; Chao-ke Tang] Institute;[Zhong-Cheng Mo; Ji Xiao; Zhi-feng Long; Guang-hui Yi; Feng Yao; Yu-lin Tan; Min Zhang; Guo-jun Zhao; Chao-ke Tang] of;[Zhong-Cheng Mo; Ji Xiao; Zhi-feng Long; Guang-hui Yi; Feng Yao; Yu-lin Tan; Min Zhang; Guo-jun Zhao; Chao-ke Tang] Cardiovascular;[Zhong-Cheng Mo; Ji Xiao; Zhi-feng Long; Guang-hui Yi; Feng Yao; Yu-lin Tan; Min Zhang; Guo-jun Zhao; Chao-ke Tang] Research,;[Zhong-Cheng Mo; Ji Xiao; Zhi-feng Long; Guang-hui Yi; Feng Yao; Yu-lin Tan; Min Zhang; Guo-jun Zhao; Chao-ke Tang] Key
会议名称：
2014年第十二届全国脂质与脂蛋白学术会议
会议时间：
2014-10-10
会议地点：
杭州
会议主办单位：
中国生物化学与分子生物学会脂质与脂蛋白专业委员会
会议论文集名称：
2014年第十二届全国脂质与脂蛋白学术会议论文集
摘要：
<正>Objects:The aim of this study is to investigate the effects of advanced oxidation protein products(AOPPs)on ATP-binding cassette transporter A1(ABCA1)and ABCG1 expression,atherosclerotic lesion and
摘要：
目的:观察apelin-13是否通过影响ABCA1蛋白水平从而调节Aβ代谢。方法:1Western blot检测PC-12细胞血管紧张素受体AT1相关的受体蛋白(putative recep tor p rotein related to the angiotensin recep tor AT1,APJ)表达,以确定PC-12细胞存在apelin-13作用受体。2用不同浓度(1、10、100nm
摘要：
Rationale: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. Objective: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. Methods and results: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. Conclusion: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
摘要：
Background: Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. Methods and Results: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXR alpha) expression were down-regulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXR alpha expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXR alpha expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPP5-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages. Conclusions: AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXR alpha signaling pathway in apoE-KO mice.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
ATP-binding cassette transporter A1;Interleukin-12;Interleukin-18;Liver X receptor alpha;Nuclear factor-kappa B
摘要：
Background: Interleukin (IL)-18 and IL-12 synergize for the production of interferon (IFN)-γ, which can downregulate ATP-binding cassette transporter A1 (ABCA1) expression. The aim of the present study was to investigate the effect of IL-18 and/or IL-12 on ABCA1 expression. Methods and Results: IL-18 combined with IL-12 decreased ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells, whereas IL-18 or IL-12 alone had no effect. IL-12 increased IL-18 receptor (IL-18R) expression, which was suppressed by small interfering RNA (siRNA) for signal transducer and activator of transcription 3. IL-18R but not IL-12 receptor siRNA completely reversed the effects of IL-18 and IL-12 on ABCA1 expression and cellular cholesterol efflux. Treatment with IL-18 plus IL-12 markedly augmented nuclear translocation of nuclear factor (NF)-κB but had no effect on expression and activity of liver X receptor α. IL-18 and IL-12 also significantly increased zinc finger protein 202 (ZNF202) levels and IFN-γ secretion. Furthermore, siRNA for ZNF202 or IFN-γ significantly impaired IL-18/IL-12-induced suppression of ABCA1, whereas NF-κB siRNA treatment blocked IL-18/IL-12' action on ZNF202 levels, IFN-γ secretion, and ABCA1 expression. Conclusions: IL-18 and IL-12 together can decrease ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells through the IL-18R/NF-κB signaling pathway.
