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：
Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and responsible for catalyzing lipolysis of triglycerides in lipoproteins. LPL is produced mainly in adipose tissue, skeletal and heart muscle, as well as in macrophage and other tissues. After synthesized, it is secreted and translocated to the vascular lumen. LPL expression and activity are regulated by a variety of factors, such as transcription factors, interactive proteins and nutritional state through complicated mechanisms. LPL with different distributions may exert distinct functions and have diverse roles in human health and disease with close association with atherosclerosis. It may pose a pro-atherogenic or an anti-atherogenic effect depending on its locations. In this review, we will discuss its gene, protein, synthesis, transportation and biological functions, and then focus on its regulation and relationship with atherosclerosis and potential underlying mechanisms. The goal of this review is to provide basic information and novel insight for further studies and therapeutic targets. (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 (LXRα) expression were downregulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXRα expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXRα expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPPs-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-LXRα signaling pathway in apoE-KO mice. (Circ J 2014; 78: 2760–2770)
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.
作者机构：
[刘理静; 张平] Dept. of Respiration, First Affiliated Hospital, China;[于小华] Life Science Research Center, University of South China, Hengyang, Hunan 421001, China
摘要：
MicroRNAs are a group of endogenous, small non-coding RNA molecules that can induce translation repression of target genes within metazoan cells by specific base pairing with the mRNA of target genes. Recently, microRNA-33 has been discovered as a key regulator in the initiation and progression of atherosclerosis. This review highlights the impact of microRNA-33-mediated regulation in the major cardiometabolic risk factors of atherosclerosis including lipid metabolism (HDL biogenesis and cholesterol homeostasis, fatty acid, phospholipid and triglyceride, bile acids metabolism), inflammatory response, insulin signaling and glucose/energy homeostasis, cell cycle progression and proliferation, and myeloid cell differentiation. Understanding the etiology and pathophysiology of microRNA-33 in atherosclerosis may provide basic knowledge for the development of novel therapeutic targets for ameliorating atherosclerosis and cardiovascular disease.
摘要：
To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.
期刊：
BioTechnology: An Indian Journal,2013年8(4):543-550 ISSN：0974-7435
通讯作者：
Liao, D.-F.(dfliao66@aliyun.com)
作者机构：
[Tuo, Qin-Hui; Liao, Duan-Fang; Gong, Yong-Zhen; Sun, Shao-Wei] Hunan University of Chinese Medicine, Hanpu Science and Education District, 1# Xiangzui Road, Changsha 410208, Hunan, China;[Ke-Tang, Chao] Institute of Cardiovascular Disease, Life Science Research Center, University of South China, 28# Changsheng Western Road, Hengyang 421001, Hunan, China;[Tuo, Qin-Hui; Ke-Tang, Chao; Liao, Duan-Fang; Gong, Yong-Zhen; Zhang, Xiao-Ying; Sun, Shao-Wei] Division of biochemistry, School of pharmacy and Life Science, University of South China, 28# Changsheng West Road, Hengyang 421001, Hunan, China;[Zhang, Xiao-Ying] Division of Pharmacoproteomics, School of pharmacy and Life Science, University of South China, 28# Changsheng Western Road, Hengyang 421001, Hunan, China
通讯机构：
[Liao, D.-F.] H;Hunan University of Chinese Medicine, 1# Xiangzui Road, Changsha 410208, Hunan, China
摘要：
Apelin has an antiatherogenic function through activating protein kinase C (PKC) to initiate a series of cellular signaling pathways. PKC phosphorylates and stabilizes ATP-binding cassette transporter A1 (ABCA1) through inhibiting its degradation mediated by calpain. Thus, in the present study, we investigated whether apelin-13 affects expression of ABCA1 through PKC signaling. The results showed that apelin-13 dramatically increased cholesterol efflux from THP-1 macrophage-derived foam cells and reduced cellular cholesterol levels. ABCA1 protein but not mRNA levels were dramatically increased by apelin-13, and calpain-induced degradation of ABCA1 and calpain activity were suppressed with treatment of apelin-13. However, the effects of apelin-13 on ABCA1 protein expression, cellular cholesterol efflux and calpain activity were abolished by depletion of PKCα, suggesting the potential important role of PKCα. In addition, apelin-13 was shown to phosphorylate serine residues in ABCA1 through the PKCα pathway. Thus, apelin-13 appears to activate PKCα, phosphorylate ABCA1 and inhibit calpain-mediated proteolysis, thereby promoting cholesterol efflux and reducing foam cell formation. Our study herein described a possible mechanism for understanding the antiatherogenic effects of apelin on attenuating the progression of atherosclerosis.
摘要：
AIM: Apolipoprotein A-I (apoA-I), the major component of high-density lipoprotein (HDL), has been recently found to suppress inflammation. This study was to investigate the effects and potential mechanisms of apoA-I on the CD40/CD40 ligand (CD40L) proinflammatory signaling pathway. METHODS: Human THP-1 macrophage-derived foam cells were treated with sCD40L alone or in the presence of apoA-I. Secretion of proinflammatory cytokines was performed by enzyme-linked immunosorbent assay(ELISA). The proteins and mRNA expression were examined by western-blot and real-time PCR analysis, respectly. Cholesterol efflux was assessed by liquid scintillation counting. Cholesterol depletion of macrophages was performed with methylated beta-cyclodextrin. RESULTS: ApoA-I inhibits the inflammatory response stimulated by soluble CD40L (sCD40L) in macrophages. In addition, apoA-I inhibited the sCD40L-stimulated activation of nuclear factor-kB (NF-kB). The apoA-I-induced NF-kB deactivation was related to the decreased recruitment of tumor necrosis factor receptor-associated factor 6 (TRAF-6), a crucial adapter protein for CD40 in macrophages, to lipid rafts after being treated by sCD40L. When interfering the expression of ATP-binding cassette transporter A1 (ABCA1), a major cholesterol transporter for apoA-I in macrophages, it could significantly diminish the effect of apoA-I on the sCD40L-stimulated inflammatory response. CONCLUSION: ApoA-I suppresses CD40 proinflammatory signaling in macrophages by preventing TRAF-6 translocation to lipid rafts through ABCA1-dependent regulation of free cholesterol (FC) efflux, which may present a novel mechanism of apoA-I-mediated inflammation inhibition in macrophages.
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.
作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
