作者：
GONG Yong-zhen;SUN Shao-wei;SUN Xin-yuan;NIE Fang;ZHENG Xi-long;...
作者机构：
[GONG Yong-zhen; SUN Shao-wei; SUN Xin-yuan; NIE Fang; LIAO Duan-fang] Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan-Incubation,Hunan University of Chinese Medicine,Changsha 410208,China;[GONG Yong-zhen] Department of Pharmacology,School of Pharmaceutical Sciences,Central South University,Changsha 410078,China;[ZHENG Xi-long] Department of Biochemistry and Molecular Biology,University of Calgary,Calgary,Alberta,Canada
作者机构：
[Li, Shun-Xiang; Yang, Yun-Bo; Zheng, Xi-Long; Liao, Duan-Fang; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Yang, Yun-Bo; Zhu, Neng] Cent S Univ, Xiang Ya Hosp 2, Changsha, Hunan, Peoples R China.;[Qin, Li] South China Univ, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;[Zhu, Neng] South China Univ, Affiliated Hosp 2, Hengyang, Hunan, Peoples R China.;[Yang, Yun-Bo; Yang, Yi-Xin] Western Univ, London Hlth Sci Ctr, Matthew Mailing Ctr Translat Transplantat Studies, London, ON, Canada.
通讯机构：
[Liao, Duan-Fang] H;Hunan Univ Chinese Med, 1 Xiangzui Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
Ezetimibe;Inflammation;Mitogen-activated protein kinase;Nuclear factor kappa-light-chain-enhancer of activated B cells;Macrophage
摘要：
Inflammation plays a crucial role in atherosclerosis. Monocytes/ macrophages are involved in the inflammatory process during atherogenesis. Here, we performed daily gavage of ezetimibe in apolipoprotein E-deficient mice fed with a high-fat diet and found that ezetimibe administration decreased the level of C-reactive protein significantly. To investigate the potential molecular mechanism, we employed microarray analysis on the cultured macrophages treated with Chol: M beta CD in the presence or absence of ezetimibe. We found that ezetimibe dramatically down-regulated the expression of the tumor necrosis factor-a (TNF-alpha) gene. Consistent with the microarray results, TNF-alpha protein levels were inhibited by ezetimibe. Moreover, ezetimibe suppressed the promoter activity of TNF-alpha but not TNF-alpha lacking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) binding domain in THP-1 cells treated with phorbol myristate acetate and Chol: M beta CD. Furthermore, treatment of THP-1 macrophages with ezetimibe resulted in the degradation of l kappa B and subsequently inhibited nuclear translocation of NF-kappa B and its transcriptional activity. Inhibition of the mitogen-activated protein kinase (MAPK) pathway using PD98059 attenuated the reduction effect of ezetimibe on the expression of NF-kappa B. Collectively, our results demonstrated that the anti-inflammatory properties of ezetimibe in THP-1 macrophages are, at least in part, through suppression of NF-kappa B activation via the MAPK pathway. These data provide direct evidence for the potential application of ezetimibe in the prevention and treatment of inflammatory diseases. (C) 2014 S. Karger AG, Basel
摘要：
Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. Ezetimibe is a new lipid lowering agent that inhibits cholesterol absorption. In the present study we attempted to investigate whether ezetimibe has any effect on VSMC proliferation and the potential mechanisms involved. Our data showed ezetimibe abrogated the proliferation and migration of primary rat VSMCs induced by Chol:MβCD. Mechanically, we found that ezetimibe was capable of abolishing cyclin D1, CDK2, phospho-Rb (p-Rb), and E2F protein expressions that were upregulated by Chol:MβCD treatment. In addition, Ezetimibe was able to reverse cell cycle progression induced by Chol:MβCD, which was further supported by its down-regulation of cyclin D1 promoter activity in the presence of Chol:MβCD. Furthermore, ezetimibe abrogated the increment of phospho-ERK1/2 (p-ERK1/2) and nuclear accumulation of ERK1/2 in VSMCs induced by Chol:MβCD. Inhibition of the MAPK pathway by using ERK1/2 inhibitor PD98059 attenuated the reduction effect of ezetimibe on the expressions of phosphor-MEK1 (p-MEK1), p-ERK1/2, and cyclin D1. Taken together our data suggest that ezetimibe inhibits Chol:MβCD-induced VSMCs proliferation and leads to cell cycle arrest at the G0/G1 phase by suppressing cyclin D1 expression via the MAPK signaling pathway. These novel findings support the potential pleiotropic effect of ezetimibe in cardiovascular disease.
作者机构：
[Qinhui Tuo; duanfang Liao] Hunan University of Chinese Medicine, 300＃ Xueshi Rd, Hanpu District of Science and Education;[Qinhui Tuo; Shuhua Cui; Tianping Li; Juan Wen] Key Laboratory for Pharmacoproteomics, School of Life Science and Technology, University of South China;[Guozuo Xiong] Department of general surgery, the second affiliated hospital in University of South China
会议名称：
脂质组学与脂蛋白的新功能-第十二届全国脂质与脂蛋白学术会议
会议时间：
2014-01-01
会议地点：
中国浙江杭州
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：
第十二届全国脂质与脂蛋白学术会议论文汇编
摘要：
<正>To explore whether Daxx mediates Chol:MβCD induced cholesterol accumulation and apopotosis in macrophage.The eukaryotic vector of Daxx was constructed to be stably transfected into RAW264.7 cells,the mRNA and protein expressions of Daxx was quantified by RT-PCR and western blotting,respectively.Intracellular lipiddroplets and lipid levels were assayed by oil red Q staining and enzymefluorescent analysis.The growth inhibition
摘要：
Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.
