作者： Zhao, Zhen-Wang;Zhang, Min;Wang, Gang;Zou, Jin;Gao, Jia-Hui;...

期刊： JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,2021年77(2):217-227 ISSN：0160-2446

通讯作者： Yu, Xiao-Hua PhD

作者机构： [Tang, Chao-Ke; Zhao, Zhen-Wang; Zhou, Li; Wang, Gang; Zou, Jin; Gao, Jia-Hui; Wan, Xiang-Jun; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Expt Ctr,Hengyang Med Sch,Hunan Int Sci &, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang, Hunan, Peoples R China.;[Zhang, Da-Wei] Univ Alberta, Dept Pediat, Edmonton, AB, Canada.;[Zhang, Da-Wei] Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB, Canada.;[Yu, Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Hainan, Peoples R China.

通讯机构： [Yu, Xiao-Hua PhD] I;Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

关键词： 2 chloro 5 nitrobenzanilide;ABC transporter A1;ABC transporter G1;astragalin;immunoglobulin enhancer binding protein;interleukin 1beta;interleukin 6;liver X receptor alpha;monocyte chemotactic protein 1;parthenolide;peroxisome proliferator activated receptor gamma;toll like receptor 4;tumor necrosis factor;ABC transporter A1;ABCA1 protein, human;ABCA1 protein, mouse;ABCG1 protein, human;ABCG1 protein, mouse;antiinflammatory agent;astragalin;autacoid;cholesterol;kaempferol derivative;animal cell;animal experiment;animal model;animal tissue;apolipoprotein E knockout mouse;Article;atherosclerosis;atherosclerotic plaque;controlled study;drug effect;drug mechanism;foam cell;lipid metabolism;macrophage;male;mediator release;mouse;nonhuman;protein expression;upregulation;animal;atherosclerosis;disease model;genetics;HEK293 cell line;human;metabolism;pathology;THP-1 cell line;Animals;Anti-Inflammatory Agents;Atherosclerosis;ATP Binding Cassette Transporter 1;ATP Binding Cassette Transporter, Subfamily G, Member 1;Cholesterol;Disease Models, Animal;Foam Cells;HEK293 Cells;Humans;Inflammation Mediators;Kaempferols;Macrophages;Male;Mice, Knockout, ApoE;Plaque, Atherosclerotic;THP-1 Cells;Up-Regulation

摘要： Lipid metabolism disorder and inflammatory response are considered to be the major causes of atherosclerogenesis. Astragalin, the most important functional component of flavonoid obtained from persimmon leaves, has the hypolipidemic effects. However, it is unknown, how astragalin protects against atherosclerosis. The aim of this study was to observe the effects of astragalin on cholesterol efflux and inflammatory response and to explore the underlying mechanisms. Our results showed that astragalin upregulated the expression of ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1), promoted cholesterol efflux, and suppressed foam cell formation. Inhibition of the PPARγ/LXRα pathway abrogated the promotive effects of astragalin on both transporter expression and cholesterol efflux. In addition, treatment of astragalin markedly decreased the secretion of inflammatory factors, including interleukin 6, monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1β. Mechanistically, astragalin upregulated ABCA1 and ABCG1 expression, which in turn reduced TLR4 surface levels and inhibited NF-B nuclear translocation. Consistently, astragalin reduced atherosclerotic plaque area in apoE-/- mice. Taken together, these findings suggest that astragalin protects against atherosclerosis by promoting ABCA1- and ABCG1-mediated cholesterol efflux and inhibiting proinflammatory mediator release. © 2020 Wolters Kluwer Health, Inc. All rights reserved.

语种： 英文

作者： Zhao, Zhen-Wang;Zhang, Min;Liao, Ling-Xiao;Zou, Jin;Wang, Gang;...

期刊： BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,2021年1866(5):158904 ISSN：1388-1981

通讯作者： Yu, Xiao-Hua;Tang, Chao-Ke

作者机构： [Qin, Yu-Sheng; Tang, Chao-Ke; Liao, Ling-Xiao; Zhao, Zhen-Wang; Zhou, Li; Li, Heng; Wang, Gang; Zou, Jin; Wan, Xiang-Jun; Zhang, Min] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang Med Sch,Hunan Prov Cooperat Innovat Ctr, Hengyang 421001, Hunan, Peoples R China.;[Liao, Ling-Xiao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Yu, Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Hainan, Peoples R China.

通讯机构： [Yu, Xiao-Hua; Tang, Chao-Ke] I;Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 460106, China. Electronic address:;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic disease, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address:

关键词： ABCA1;LncRNA PCA3;RFX7;atherosclerosis;miR-140-5p

摘要： OBJECTIVE: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE(-/-) mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis. RESULTS: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE(-/-) mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis. CONCLUSIONS: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.

语种： 英文

作者： Hou, Kai;Li, Shuai;Zhang, Meng;Qin, Xuping*

期刊： Clinica Chimica Acta,2021年513:25-33 ISSN：0009-8981

通讯作者： Qin, Xuping

作者机构： [Qin, Xuping; Hou, Kai; Li, Shuai] Univ South China, Inst Pharm & Pharmacol, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Zhang, Meng] Univ South China, Affiliated Hosp 2, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Qin, Xuping] U;Univ South China, Inst Pharm & Pharmacol, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.

关键词： Atherosclerosis;Autophagy;Caveolin-1;Inflammatory response;Lipid metabolism

摘要： Caveolin-1 is considered an important pathophysiological factor in atherosclerosis development. Previous studies indicate that caveolin-1 exhibits a pathogenic capacity in atherosclerosis via the regulation of membrane trafficking, cholesterol metabolism and cellular signal transduction. Accumulating evidence shows that autophagy activation influences the progression and development of atherosclerosis in multiple ways, including cholesterol metabolism, inflammatory responses and lipid transcytosis. However, how caveolin-1 is involved in autophagy activation in atherosclerosis remains unclear, and the precise mechanisms of caveolin-1 on autophagic flux in atherosclerosis need to be further investigated. Clarifying the roles and mechanisms of caveolin-1 in the regulation of autophagy activation is of great importance, contributing to the ability to manipulate caveolin-1 as a novel therapeutic approach for atherosclerosis. In this review, we summarize the understanding of the molecular structure, biological roles and biochemical functions of caveolin-1 to date and discuss the roles and mechanisms of caveolin-1 in autophagy activation. The emphasis on the potential of caveolin-1 to be a novel therapeutic target in atherosclerosis and understanding its precise functions and exact mechanisms in autophagic flux will provide evidence for future experimental research and aid in the development of novel therapeutic strategies for atherosclerosis.

语种： 英文

作者： Cao, Zhao-Hui;Wu, Zhuan;Hu, Cong;Zhang, Min;Wang, Wu-Zhou;...

期刊： 中华医学杂志(英文版),2020年133(1):68-73 ISSN：0366-6999

通讯作者： Hu, Xiao-Bo

作者机构： [Hu, Cong; Wang, Wu-Zhou; Cao, Zhao-Hui; Hu, Xiao-Bo; Wu, Zhuan; Zhang, Min] Univ South China, Hengyang Med Coll, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Hu, Xiao-Bo] U;Univ South China, Hengyang Med Coll, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.

关键词： Endoplasmic reticulum stress;Inflammation;Autoimmunity;Type 1 diabetes

摘要： OBJECTIVE: Type 1 diabetes (T1D) results from dysfunction of pancreatic islets beta cells. Recent studies supported that endoplasmic reticulum (ER) stress takes an important role in pancreatic beta cell excessive loss, resulting in T1D. Here, we aimed to review the relationship between ER stress and T1D. Additionally, we also reviewed the potential mechanisms underlying ER stress mediated T1D. DATA SOURCES: This review was based on the articles from PubMed databases up to July 2019, with the following keywords: "endoplasmic reticulum stress", "inflammation", "autoimmunity", and "type 1 diabetes". STUDY SELECTION: Original articles and critical reviews on the topics were selected and carefully analyzed. RESULTS: Studies have shown that severe ER stress is directly involved in the pancreatic beta cells destruction and pathogenesis of T1D. CONCLUSIONS: ER stress plays a key part in pancreatic beta cells and T1D, which will help in developing new effective therapeutics for T1D.

语种： 英文

作者： Zhang, Cai-Ping;Ding, Xin-Xin;Tian, Tian;Li, Bo-Jie;Wang, Chu-Yao;...

期刊： MOLECULAR MEDICINE REPORTS,2020年22(4):2665-2672 ISSN：1791-2997

通讯作者： Zhang, Min;Long, Shi-Yin

作者机构： [Shao, Jin-Qi; Ding, Xin-Xin; Wang, Chu-Yao; Tian, Ying; Long, Shi-Yin; Zhang, Cai-Ping; Yuan, Yu-Lin; Zhang, M; Long, SY; Li, Bo-Jie; Jiang, Su-Su; Zhang, Min] Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Ding, Xin-Xin] Second People Hosp Dezhou, Dept Pathol, Dezhou 253000, Shandong, Peoples R China.;[Tian, Tian] First Hosp Changsha, Dept Clin Lab, Changsha 410005, Hunan, Peoples R China.

通讯机构： [Zhang, M; Long, SY] U;Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： oxidized low density lipoprotein;low density lipoprotein;oxidized low density lipoprotein;apoptosis;Article;autophagy (cellular);controlled study;coronary artery atherosclerosis;electron microscopy;endothelium cell;human;human cell;human cell culture;HUVEC cell line;lipid storage;lipophagocytosis;long term exposure;lysosome;MTT assay;oxidative stress;transmission electron microscopy;Western blotting;autophagy;cell line;cell survival;cytology;drug effect;lipid metabolism;metabolism;umbilical vein endothelial cell;Autophagy;Cell Line;Cell Survival;Human Umbilical Vein Endothelial Cells;Humans;Lipid Metabolism;Lipoproteins, LDL;Microscopy, Electron;Oxidative Stress

摘要： Oxidative stress induces the formation of oxidized low-density lipoprotein (ox-LDL ), which accelerates the development of atherosclerosis and the rupture of atherosclerotic plaques by promoting lipid accumulation and inhibiting autophagy in vascular cells. Lipophagy is known to be involved in maintaining the balance of neutral lipid metabolism; however, the phenomenon of lipophagy deficiency in ox-LDL- treated endothelial cells (EC s) remains to be elucidated. It has been demonstrated that lipid accumulation caused by ox-LDL inhibits autophagy, which promotes apoptosis in EC s. The aim of the present study was to investigate the association between decreased autophagy and lipid accumulation in EC s treated with ox-LDL . Electron microscopy demonstrated that the formation of autolipophagosomes was decreased in ox-LDL- treated human umbilical vein EC s compared with that in the LDL- treated group and was accompanied by a decrease in the autophagy-associated proteins via western blotting analysis. Using laser focal colocalization detection, decreased lipid processing was observed in the lysosomes of ox-LDL- treated EC s, which indicated that lipophagy may be attenuated and subsequently result in lipid accumulation in ox-LDL- treated EC s. © 2020 Spandidos Publications. All rights reserved.

语种： 英文

作者： Yang, Hui-xian;Zhang, Min;Long, Shi-yin;Tuo, Qin-hui;Tian, Ying;...

期刊： Clinica Chimica Acta,2020年500:81-86 ISSN：0009-8981

通讯作者： Zhang, Cai-ping;Liao, DF

作者机构： [Yang, Hui-xian] Univ South China, Med Coll, Inst Cardiovasc Dis, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang; Chen, Jian-xiong; Tuo, Qin-hui] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Liao, DF; Tian, Ying; Long, Shi-yin; Yang, Hui-xian; Zhang, Cai-ping; Zhang, Min] Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Jian-xiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, University, MS 38677 USA.

通讯机构： [Liao, DF ; Zhang, CP] U;Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： Dyslipidemia;IDOL;LDL-C;LDLR;PCSK9;SREBP2

摘要： The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.

语种： 英文

作者： 马云;罗应;谭华欣;张敏;何淑雅

期刊： 教育教学论坛,2019年(4):146-148 ISSN：1674-9324

作者机构： 南华大学生物化学与分子生物学研究所,湖南 衡阳,421001;[何淑雅; 谭华欣; 罗应; 张敏; 马云] 南华大学

关键词： 案例教学;医学分子生物学;教学改革

摘要： 以提升教学质量、培养卓越医生为目的,笔者将案例教学法应用到本校医学专业本科生的医学分子生物学课程教学中。目前分子生物学的理论和技术已在医学领域得到广泛应用,因此医学分子生物是医学院校学生的一门非常重要的课程。通过教学实践证明,案例教学法激发了学生的学习兴趣,提高了学生的自学能力、思考分析及解决问题能力、语言组织及表达能力和创新思维意识,提高了课堂学习的效率,为医学分子生物学的教学改革提供了一条有效途径。

语种： 中文

作者： Hu, Xiaobo;Hu, Cong;Zhang, Caiping;Zhang, Min;Long, Shiyin;...

期刊： International braz j urol,2019年45(2):220-228 ISSN：1677-5538

通讯作者： Cao, Zhaohui

作者机构： [Cao, Zhaohui; Hu, Xiaobo] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Hu, Cong; Cao, Zhaohui; Hu, Xiaobo; Long, Shiyin; Zhang, Caiping; Zhang, Min] Univ South China, Sch Pharm & Biosci, Dept Biotechnol, Hengyang, Peoples R China.

通讯机构： [Cao, Zhaohui] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.

关键词： Prostatic Neoplasms;Obesity;Stress, Physiological

摘要： Obesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy.

语种： 英文

作者： Zhang, Mengxia;Liu, Qi;Li, Lijun;Ning, Jing;Tu, Jian;...

期刊： ONCOLOGY REPORTS,2019年41(3):1807-1816 ISSN：1021-335X

通讯作者： Tang, SS

作者机构： [Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, SS; Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.

通讯机构： [Tang, SS ] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.

关键词： caspase 3;caspase 9;colony stimulating factor 1;doxorubicin;hoe 33342;hypoxia inducible factor 1alpha;protein Bax;protein BNip3;antineoplastic antibiotic;BAX protein, human;BCL2 protein, human;BNIP3 protein, human;colony stimulating factor 1;CSF1 protein, human;doxorubicin;HIF1A protein, human;hypoxia inducible factor 1alpha;membrane protein;oncoprotein;protein Bax;protein bcl 2;antiapoptotic activity;apoptosis;Article;binding affinity;controlled study;down regulation;flow cytometry;human;human cell;immunoprecipitation;MCF-7 cell line;priority journal;protein expression;protein protein interaction;signal transduction;upregulation;Western blotting;apoptosis;breast tumor;drug effect;drug resistance;female;MCF-7 cell line;metabolism;multidrug resistance;pathology;signal transduction;Antibiotics, Antineoplastic;Apoptosis;bcl-2-Associated X Protein;Breast Neoplasms;Doxorubicin;Drug Resistance, Multiple;Drug Resistance, Neoplasm;Female;Humans;Hypoxia-Inducible Factor 1, alpha Subunit;Macrophage Colony-Stimulating Factor;MCF-7 Cells;Membrane Proteins;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-bcl-2;Signal Transduction

摘要： Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1α (HIF-1α)/BCL2/adeno-virus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1α, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M‑CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1α/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds. © 2019 Spandidos Publications. All rights reserved.

语种： 英文

作者： Xie, Wei;Li, Liang;Gong, Duo;Zhang, Min;Lv, Yun-Cheng;...

期刊： Ateroskleroz,2019年289:143-161 ISSN：2078-256X

通讯作者： Yin, Wei-Dong;Tang, Chao-Ke

作者机构： [Gong, Duo; Zhang, Min; Tang, Chao-Ke; Zhao, Zhen-Wang; Li, Liang; Yin, Wei-Dong; Xie, Wei] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov,Med Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Lv, Yun-Cheng; Xie, Wei; Guo, Dong-ming] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Dept Pathophysiol, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Cumming Sch Med, Dept Biochem & Mol Biol,Libin Cardiovasc Inst Alb, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.;[Zheng, Xi-Long] Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Targets & Clin Pharmacol, Guangzhou 511436, Guangdong, Peoples R China.

通讯机构： [Yin, WD; Tang, CK] U;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.

关键词： cholesterol;cholesterol ester;gypenoside;high density lipoprotein cholesterol;interleukin 1beta;interleukin 6;kruppel like factor 4;lipoprotein lipase;low density lipoprotein cholesterol;messenger RNA;microRNA;microRNA 27a;monocyte chemotactic protein 1;oxidized low density lipoprotein;tumor necrosis factor;unclassified drug;gypenoside;Klf14 protein, mouse;kruppel like factor;lipid;lipoprotein lipase;low density lipoprotein;microRNA;Mirn27 microRNA, mouse;plant extract;animal cell;animal experiment;animal model;animal tissue;aortic atherosclerosis;Article;atherosclerotic plaque;binding site;cell viability;cholesterol blood level;controlled study;cytokine release;down regulation;gene expression regulation;high density lipoprotein cholesterol level;human;human cell;human tissue;in vitro study;in vivo study;inflammation;lipid homeostasis;lipid metabolism;lipid storage;low density lipoprotein cholesterol level;macrophage function;male;mouse;mRNA expression level;nonhuman;peritoneum macrophage;priority journal;promoter region;protein expression level;THP-1 cell line;upregulation;animal;apolipoprotein E knockout mouse;atherosclerosis;chemistry;down regulation;genetic transfection;Gynostemma;homeostasis;lipid metabolism;macrophage;metabolism;pathology;RAW 264.7 cell line;Animals;Atherosclerosis;Down-Regulation;Gene Expression Regulation, Enzymologic;Gynostemma;Homeostasis;Kruppel-Like Transcription Factors;Lipid Metabolism;Lipids;Lipoprotein Lipase;Lipoproteins, LDL;Macrophages;Male;Mice;Mice, Knockout, ApoE;MicroRNAs;Plant Extracts;RAW 264.7 Cells;Transfection

摘要： Background and aims: Krüppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. Methods and results: mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE−/−) mice. Conclusions: KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation. © 2019 Elsevier B.V.

语种： 英文

作者： Tan, Yu-lin;Ou, Han-xiao;Zhang, Min;Gong, Duo;Zhao, Zhcn-wang;...

期刊： CURRENT PHARMACEUTICAL BIOTECHNOLOGY,2019年20(5):422-432 ISSN：1389-2010

通讯作者： Mo, Zhong-cheng;Tang, Chao-ke

作者机构： [Gong, Duo; Tang, Chao-ke; Tan, Yu-lin; Zhao, Zhcn-wang; Chen, Ling-yan; Xia, Xiao-dan; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Dis, Med Res Ctr,Key Lab Arterosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Tan, Yu-lin] XiangNan Univ, Inst Pathol Res, Dept Pathophysiol, Key Disciplines Immunol,Key Lab Nat Cardiovasc Me, Chenzhou 423000, Peoples R China.;[Ou, Han-xiao; Mo, Zhong-cheng] Univ South China, Cooperat Innovat Base Basic & Clin Med, Hengyang 414000, Hunan, Peoples R China.;[Ou, Han-xiao; Mo, Zhong-cheng] Yueyan Matern Child Hlth Hosp, Dept Genet & Eugen, Hengyang 414000, Hunan, Peoples R China.;[Ou, Han-xiao; Mo, Zhong-cheng] Univ South China, Sch Med, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang, Peoples R China.

通讯机构： [Mo, ZC; Tang, CK] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Key Lab Arterosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.

关键词： Tan IIA;Omentin-1;ABCA1;cholesterol efflux;reverse cholesterol transport;plaque vulnerability.

摘要： <jats:sec><jats:title>Background:</jats:title><jats:p>Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated.</jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p>To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE−/− mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE−/− mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE−/− mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE−/− mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1.</jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p>Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.</jats:p></jats:sec>

语种： 英文

作者： Ye, Qiong;Tian, Guo-Ping;Cheng, Hai-Peng;Zhang, Xin;Ou, Xiang;...

期刊： Journal of Atherosclerosis and Thrombosis,2018年25(3):244-253 ISSN：1340-3478

通讯作者： Tang, Chao-Ke

作者机构： [Zhang, Xin; Gong, Duo; Cheng, Hai-Peng; Ye, Qiong; Xia, Xiao-Dan; Zhang, Min; Tang, Chao-Ke; Zhao, Zhen-Wang; Yu, Xiao-Hua; Li, Liang; Xie, Wei; Huang, Chong; Chen, Ling-Yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang, Hunan, Peoples R China.;[Tan, Ru-Qi; Ye, Qiong; Tian, Guo-Ping; Yang, Feng-Yun; Pan, Yan-Jun] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Ou, Xiang] First Hosp Changsha, Dept Endocrinol, Changsha, Hunan, Peoples R China.;[Zhang, Jie] Univ South China, Affiliated Hosp 2, Dept Spinal Surg, Hengyang, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Cumming Sch Med,Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB, Canada.

通讯机构： [Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.

关键词： angiopoietin related protein 4;apolipoprotein E;high density lipoprotein cholesterol;interleukin 1beta;interleukin 6;low density lipoprotein cholesterol;microRNA;microRNA 134;monocyte chemotactic protein 1;tumor necrosis factor;unclassified drug;angiopoietin related protein 4;Angptl4 protein, mouse;cholesterol;cytokine;lipid;lipoprotein lipase;microRNA;MIRN132 microRNA, mouse;analysis of variance;animal experiment;animal model;animal tissue;Article;atherosclerosis;body weight;chromatin immunoprecipitation;connective tissue;controlled study;cytokine production;gene overexpression;high performance liquid chromatography;incubation temperature;inflammation;lipid diet;lipid storage;macrophage;male;microscopy;mortality;mouse;nonhuman;observational study;peritoneum macrophage;protein expression;real time polymerase chain reaction;receptor upregulation;reverse transcription polymerase chain reaction;signal transduction;Western blotting;animal;apolipoprotein E knockout mouse;atherosclerosis;blood;C57BL mouse;chemistry;foam cell;genetics;metabolism;Angiopoietin-like 4 Protein;Animals;Atherosclerosis;Cholesterol;Cytokines;Foam Cells;Inflammation;Lipids;Lipoprotein Lipase;Macrophages;Male;Mice;Mice, Inbred C57BL;Mice, Knockout, ApoE;MicroRNAs

摘要： Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. Methods: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Results: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. Conclusions: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease. © 2018 Japan Atherosclerosis Society.

语种： 英文

作者： Zhang, Min;Zhao, Guo-Jun;Yin, Kai;Xia, Xiao-Dan;Gong, Duo;...

期刊： Circulation Journal,2018年82(5):1396-1404 ISSN：1346-9843

通讯作者： Tang, Chao-Ke;Tang, Xiao-Er

作者机构： [Gong, Duo; Tang, Chao-Ke; Zhao, Zhen-Wang; Yin, Kai; Chen, Ling-Yan; Xia, Xiao-Dan; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Dis,Med Res Ctr, Hengyang, Hunan, Peoples R China.;[Zhao, Guo-Jun] Guilin Med Univ, Dept Histol & Embryol, Guilin, Guangxi, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada.;[Zheng, Xi-Long] Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Targets & Clin Pharmacol, Guangzhou, Guangdong, Peoples R China.;[Tang, Xiao-Er] Shaoyang Univ, Dept Pathophysiol, Shaoyang, Hunan, Peoples R China.

通讯机构： [Tang, Chao-Ke] U;[Tang, Xiao-Er] S;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;Shaoyang Univ, Coll Med, Dept Pathophysiol, Shaoyang 422000, Hunan, Peoples R China.

关键词： Apolipoprotein A-1 (apoA-1);Apolipoprotein A-1 binding protein (AIBP);ATP-binding cassette transporter A1 (ABCA1);Atherosclerosis;Inflammation

摘要： Background: It has previously been demonstrated that apolipoprotein A-1 (apoA-1) binding protein (AIBP) promotes apoA-1 binding to ATP-binding cassette transporter A1 (ABCA1) and prevents ABCA1 protein degradation so as to inhibit foam cell formation. Because apoA-1 inhibits inflammatory signaling pathways, whether AIBP has an inhibitory effect on inflammatory signaling pathways in THP-1-derived macrophages is investigated. Methods and Results: Analysis of inflammation-related gene expression indicated that AIBP decreased lipopolysaccharide (LPS)- mediated macrophage inflammation. AIBP significantly prevented NF-κB nuclear translocation. Further, AIBP prevented the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular-signal regulated kinase and c-Jun N-terminal kinase. AIBP decreased MyD88 expression at both mRNA and protein levels, but did not have any effect on TLR4 expression. Moreover, treatment with both AIBP and apoA-1 decreased the abundance of TLR4 in the lipid raft fraction. AIBP lacking 115-123 amino acids (Ɗ115-123), however, did not have such effects as described for intact AIBP. In addition, knockdown of ABCA1 inhibited the effects of AIBP on inflammatory factor secretion. Conclusions: These results suggest that AIBP inhibits inflammatory signaling pathways through binding to apoA-1 and stabilizing ABCA1, and subsequent alteration of lipid rafts and TLR4 in the cell membrane. © 2018, Japanese Circulation Society. All rights reserved.

语种： 英文

作者： Cheng, Hai-Peng;Gong, Duo;Zhao, Zhen-Wang;He, Ping-Ping;Yu, Xiao-Hua;...

期刊： Circulation Journal,2018年82(1):28-38 ISSN：1346-9843

通讯作者： Yin, Wei-Dong;Tang, Chao-Ke

作者机构： [Gong, Duo; Cheng, Hai-Peng; He, Ping-Ping; Ouyang, Xin-Ping; Xia, Xiao-Dan; Zhang, Min; Tang, Chao-Ke; Tan, Yu-Lin; Zhao, Zhen-Wang; Yu, Xiao-Hua; Li, Liang; Yin, Wei-Dong; Xie, Wei; Huang, Chong; Chen, Ling-Yan] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.;[Zhang, Xin; Wang, Zong-bao] Univ South China, Sch Pharm & Life Sci Coll, Hengyang, Hunan, Peoples R China.;[Ye, Qiong; Tian, Guo-Ping] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Hengyang, Hunan, Peoples R China.;[Ye, Qiong; Tian, Guo-Ping] Univ South China, Dept Cardiovasc Med, Affiliated Hosp 2, Hengyang, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Libin Cardiovasc Inst Alberta, Cumming Sch Med, Dept Biochem & Mol Biol,Hlth Sci Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.

通讯机构： [Yin, WD; Tang, CK] U;Univ South China, Inst Cardiovasc Res, 28 W Chengsheng Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： Atherosclerosis;Histone deacetylase 9 (HDAC9);Inflammation;Lipoprotein lipase (LPL);MicroRNA-182

摘要： Background: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis. Methods and Results: Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targeting HDAC9 in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. Conclusions: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targeting HDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice. © 2017, Japanese Circulation Society. All rights reserved.

语种： 英文

作者： Zhao, Zhen-Wang;Zhang, Min;Chen, Ling-Yan;Cong, Duo;Xia, Xiao-Dan;...

期刊： BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,2018年1863(8):806-822 ISSN：1388-1981

通讯作者： Tang, Chao-Ke

作者机构： [Ou, Xiang; Tang, Chao-Ke; Cong, Duo; Zhao, Zhen-Wang; Wang, Si-Qi; Yu, Xiao-Hua; Chen, Ling-Yan; Xia, Xiao-Dan; Zhang, Min] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Med Res Expt Ct, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Ou, Xiang] First Hosp Changsha, Dept Endocrinol, Changsha 410005, Hunan, Peoples R China.;[Dai, Xiao-Yan] Guangzhou Med Univ, Guangdong Prov Key Lab Mol Target & Clin Pharmaco, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;[Dai, Xiao-Yan] Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Hlth Sci Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.

通讯机构： [Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Med Res Expt Ct, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.

关键词： HSP70;Atherosclerosis;Cholesterol efflux;ABCA1;ABCG1;Reverse cholesterol transport

摘要： Background and aims: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE−/− mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis. Methods: HSP70 was overexpressed in apoE−/− mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE−/− mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [3H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT). Results: Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE−/− mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE−/− mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE−/− mice. Conclusions: HSP70 promotes the progression of atherosclerosis in apoE−/− mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway. © 2018 Elsevier B.V.

语种： 英文

作者： Zhang, Min;Zhao, Guo-Jun;Yao, Feng;Xia, Xiao-Dan;Gong, Duo;...

期刊： Ateroskleroz,2018年273:122-130 ISSN：2078-256X

通讯作者： Tang, Chao-Ke;Tang, Xiao-Er

作者机构： [Gong, Duo; Tang, Chao-Ke; Zhao, Zhen-Wang; Yao, Feng; Chen, Ling-Yan; Xia, Xiao-Dan; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Guo-Jun] Guilin Med Univ, Dept Histol & Embryol, 1 Zhiyuan Rd, Guilin 541100, Guangxi, Peoples R China.;[Tang, Xiao-Er] Shaoyang Univ, Dept Pathophysiol, Shaoyang 422000, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.;[Tang, Chao-Ke] Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Tang, Chao-Ke] U;[Tang, Xiao-Er] S;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;Shaoyang Univ, Dept Pathophysiol, Med Coll, Shaoyang 422000, Hunan, Peoples R China.

关键词： ABC transporter A1;amino acid;apolipoprotein A1;apolipoprotein a1 binding protein;arg 1 protein;CXCL1 chemokine;CXCL2 chemokine;high density lipoprotein;immunoglobulin enhancer binding protein;intercellular adhesion molecule 1;monocyte chemotactic protein 1;mrc 1 protein;protein;unclassified drug;vascular cell adhesion molecule 1;apolipoprotein E;AUNIP protein, human;cholesterol;DNA binding protein;animal experiment;aorta;apolipoprotein E knockout mouse;Article;atherosclerosis;atherosclerotic plaque;cholesterol transport;controlled study;feces;human;in vivo study;inflammation;lipid storage;liver;macrophage;male;mouse;nonhuman;peritoneum macrophage;plasma;priority journal;animal;atherosclerosis;drug effect;genetics;inflammation;metabolism;physiology;transport at the cellular level;Animals;Apolipoproteins E;Atherosclerosis;Biological Transport;Cholesterol;DNA-Binding Proteins;Inflammation;Male;Mice

摘要： Background and aims: ApoA-1 binding protein (AIBP) is a secreted protein that interacts with apoA-I and accelerates cholesterol efflux from cells. We have recently reported that AIBP promotes apoA-1 binding to ABCA1 in the macrophage cell membrane, partially through 115–123 amino acids. However, the effects of AIBP on the development of atherosclerosis in vivo remain unknown. Methods: ApoE−/− mice with established atherosclerotic plaques were infected with rAAV-AIBP or rAAV-AIBP(Δ115-123), respectively. Results: AIBP-treated mice showed reduction of atherosclerotic lesion formation, increase in circulating HDL levels and enhancement of reverse cholesterol transport to the plasma, liver, and feces. AIBP increased ABCA1 protein levels in aorta and peritoneal macrophages. Furthermore, AIBP could diminish atherosclerotic plaque macrophage content and the expression of chemotaxis-related factors. In addition, AIBP prevented macrophage inflammation by inactivating NF-κB and promoted the expression of M2 markers like Mrc-1 and Arg-1. However, lack of 115–123 amino acids of AIBP(Δ115-123) had no such preventive effects on the progression of atherosclerosis. Conclusions: Our observations demonstrate that AIBP inhibits atherosclerosis progression and suggest that it may be an effective target for prevention of atherosclerosis. © 2018 Elsevier B.V.

语种： 英文

作者： Kuang, Hai-Jun;Zhao, Guo-Jun;Chen, Wu-Jun;Zhang, Min;Zeng, Gao-Feng;...

期刊： European Journal of Pharmacology,2017年810(1):57-62 ISSN：0014-2999

通讯作者： Tang, Chao-Ke

作者机构： [Tang, Chao-Ke; Chen, Wu-Jun; Kuang, Hai-Jun; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Guo-Jun] Guilin Med Univ, Dept Histol & Embryol, 1 Zhiyuan Rd, Guilin 541100, Guangxi, Peoples R China.;[Kuang, Hai-Jun; Zeng, Gao-Feng] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.

通讯机构： [Tang, Chao-Ke] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.

关键词： ABCA1;Atherosclerosis;Cholesterol efflux;Hsp27

摘要： Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells. Expression of antisense or 3A Hsp27 suppressed the expression of ABCA1 and cholesterol efflux. Furthermore, over-expression of wild-type and 3D Hsp27 significantly increased the levels of phosphorylated specificity protein 1 (Sp1), protein kinase C ζ (PKCζ) and phosphatidylinositol 3-kinase (PI3K). In addition, the up-regulation of ABCA1 expression and cholesterol efflux induced by 3D Hsp27 was suppressed by inhibition of Sp1, PKCζ and PI3K with specific kinase inhibitors. Taken together, our results revealed that Hsp27 may up-regulate the expression of ABCA1 and promotes cholesterol efflux through activation of the PI3K/PKCζ/Sp1 signal pathway in THP-1 macrophage-derived foam cells. Our findings may partly explain the mechanisms underlying the anti-atherogenic effect of Hsp27. © 2017 Elsevier B.V.

语种： 英文

作者： 张敏;丁新新;罗应;龙石银

期刊： 西部素质教育,2017年3(18):98-99 ISSN：2095-6401

作者机构： 南华大学药学与生物科学学院生物化学与分子生物学教研室,湖南 衡阳,421001;[罗应; 龙石银; 张敏; 丁新新] 南华大学

关键词： 生物技术专业;新生;大学适应性;班主任工作

摘要： 文章基于对生物技术专业新生适应性的调查,提出了班主任应该通过高年级学生帮助学生迅速适应新的环境,引导学生养成正确的学习观念和学习方法,帮助学生树立"完善自我,追求卓越"的精神理念,以及培养学生良好的行为方式.

语种： 中文

作者： Luo, Ying;Shen, Hai-Yan;Shen, Qing-Xiang;Cao, Zhao-Hui;Zhang, Min;...

期刊： 亚洲天然物产研究(英文版),2017年19(9):869-876 ISSN：1028-6020

通讯作者： Tan, Jian-Wen

作者机构： [Luo, Ying; Long, Shi-Yin; Wang, Zong-Bao; Cao, Zhao-Hui; Zhang, Min] Univ South China, Sch Pharm & Biol Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Educ Dept, Hengyang 421001, Peoples R China.;[Luo, Ying; Tan, Jian-Wen] Chinese Acad Sci, South China Bot Garden, Guangdong Prov Key Lab Appl Bot, Guangzhou 510650, Guangdong, Peoples R China.;[Shen, Hai-Yan] Univ South China, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;[Shen, Qing-Xiang] Univ South China, Affiliated Hosp 2, Dept Obstet & Gynaecol, Hengyang 421001, Peoples R China.

通讯机构： [Tan, Jian-Wen] C;Chinese Acad Sci, South China Bot Garden, Guangdong Prov Key Lab Appl Bot, Guangzhou 510650, Guangdong, Peoples R China.

关键词： 1,2,6 trihydroxy 5 methoxyto 9,10 anthraquinone;2 hydroxy 1 methoxyanthraquinone;2 hydroxyanthraquinone;6 hydroxy 7 methoxydehydroiso alpha lapachone;acarbose;alpha glucosidase;alpha glucosidase inhibitor;anthraquinone derivative;antibiotic agent;digiferruginol;kanamycin;naphthoquinone;plant extract;unclassified drug;1,2,6-trihydroxy-5-methoxy-9,10-anthraquinone;alpha glucosidase;anthraquinone derivative;antiinfective agent;glycosidase inhibitor;herbaceous agent;naphthoquinone;antibacterial activity;Article;Bacillus cereus;Bacillus subtilis;carbon nuclear magnetic resonance;controlled study;drug structure;electrospray mass spectrometry;enzyme inhibition;Escherichia coli;heteronuclear multiple bond correlation;IC50;in vitro study;methicillin resistant Staphylococcus aureus;minimum inhibitory concentration;nonhuman;phytochemistry;proton nuclear magnetic resonance;Rubiaceae;Salmonella enterica serovar Typhimurium;Shigella dysenteriae;Spermacoce latifolia;Staphylococcus aureus;chemical structure;chemistry;drug effects;isolation and purification;microbial sensitivity test;Rubiaceae;alpha-Glucosidases;Anthraquinones;Anti-Bacterial Agents;Bacillus cereus;Bacillus subtilis;Drugs, Chinese Herbal;Escherichia coli;Glycoside Hydrolase Inhibitors;Inhibitory Concentration 50;Methicillin-Resistant Staphylococcus aureus;Microbial Sensitivity Tests;Molecular Structure;Naphthoquinones;Rubiaceae;Salmonella typhimurium;Shigella dysenteriae

摘要： A phytochemical study on the whole plant of Spermacoce latifolia led to the isolation of a new anthraquinone, 1,2,6-trihydroxy-5-methoxy-9,10-anthraquinone (1), and a new naphthoquinone, (2R)-6-hydroxy-7-methoxy-dehydroiso-α-lapachone (2), together with three known anthraquinones (3–5). Their structures were established on the basis of detailed spectroscopic analysis, including one- and two-dimensional NMR, ESI–MS, and HR–ESI–MS techniques. All the compounds were isolated from S. latifolia for the first time. Compounds 1, 2, 4, and 5 showed significant antibacterial activity toward Bacillus subtilis with MIC values ranging from 0.9 to 31.2μg/ml, and compound 4 aslo exhibited antibacterial activity against Bacillus cereus with a MIC value 62.5μg/ml. Compound 1 was further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 value of 0.653mM. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

语种： 英文

作者： Zhang, Xin;Ye, Qiong;Gong, Duo;Lv, Yuan;Cheng, Haipeng;...

期刊： 生物化学与生物物理学报,2017年49(6):530-540 ISSN：1672-9145

通讯作者： Wang, Zongbao;Tang, Chaoke

作者机构： [Zhang, Xin; Gong, Duo; Zhao, Zhenwang; Wei, Xie; Wang, Zongbao; Chen, Lingyan; Ye, Qiong; Tang, Chaoke; Cheng, Haipeng; Zhang, Min; Yu, Xiaohua; Wang, ZB; Tang, CK; Li, Liang; Xia, Xiaodan; Lv, Yuan; Huang, Chong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Med Res Ctr, Hengyang 421001, Peoples R China.;[Zhang, Xin; Wang, Zongbao; Lv, Yuan; Wang, Shuzhi] Univ South China, Sch Pharm & Life Sci, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Ye, Qiong] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang 421001, Peoples R China.;[Zheng, Xilong] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol,Cumming Sch Med, Calgary, AB T2N 4N1, Canada.

通讯机构： [Wang, ZB; Tang, CK; Wang, Zongbao] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Med Res Ctr, Hengyang 421001, Peoples R China.;Univ South China, Sch Pharm & Life Sci, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.

关键词： apelin-13;PKCα;miR-361-5p;LPL;atherosclerosis

摘要： Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3' UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKC alpha. Taken together, our results showed that apelin-13 down-regulated the expression of LPL via activating the APJ/PKC alpha/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.

语种： 英文