动脉粥样硬化是由多种因素共同作用导致的血管壁的免疫炎症性疾病,是众多心血管疾病发生的主要病理基础。目前比较公认的动脉粥样硬化发生机制是"炎症反应"学说,即低密度脂蛋白(low density lipoprotein,LDL)中所包含的载脂蛋...动脉粥样硬化是由多种因素共同作用导致的血管壁的免疫炎症性疾病,是众多心血管疾病发生的主要病理基础。目前比较公认的动脉粥样硬化发生机制是"炎症反应"学说,即低密度脂蛋白(low density lipoprotein,LDL)中所包含的载脂蛋白ApoB-100的异常增高引起的病理性炎症反应是导致动脉粥样硬化的主要因素。通过免疫疗法抑制ApoB-100导致的病理性炎症反应,有望延缓动脉粥样硬化的发生与发展。该文主要围绕ApoB-100疫苗以及其他ApoB-100抑制剂的最新进展和存在的问题进行综述。展开更多
Apolipoprotein B100（apoB-100） is a major protein of the cholesterol-rich low-density lipoprotein（LDL） and reflects a better assessment of total atherogenic burden to the vascular system than LDL.In this work,a sim...Apolipoprotein B100（apoB-100） is a major protein of the cholesterol-rich low-density lipoprotein（LDL） and reflects a better assessment of total atherogenic burden to the vascular system than LDL.In this work,a simple and sensitive method has been developed to determine picoliter apoB-100s using the PMMA microfluidic chip coupled with electrochemical detection system. This method performs very well with a detectable linear range of 1-800 pg/mL and a detection limit of 1 pg/mL.A real serum sample has further been detected by this microchip-based biosensor.The results show that this kind of method is practicable and has the potential application in clinical analysis and diagnosis.展开更多
Background Less studies were done to compare the lipid ratios including ApoB100/ApoA1, LDL-C/HDL- C,TC/HDL-Cin elderly. So the study was to investigate the relationship between Apolipoprotein B100/ApoA1 ratio and coro...Background Less studies were done to compare the lipid ratios including ApoB100/ApoA1, LDL-C/HDL- C,TC/HDL-Cin elderly. So the study was to investigate the relationship between Apolipoprotein B100/ApoA1 ratio and coronary artery disease （CAD） in elderly. Methods 498 participants aged over 65 years with chest pain had been subsumed from Sep. 2009 to April 2011 of Guangdong General Hospital. Clinic informations of gender, age, history of hypertension, diabetes mellitus, smoking was collected. Simultaneously, serum lipids should be phlebotomized in 24 hours after be inpatient. ApoB100/ApoA1 ratio, LDL-C/HDL-C ratio. TC/HDL-C ratio, non-HDL-C were calculated using the above data. Accroding to the mean of ApoB100/ApoA1 ratio, ApoB100, non-HDL-C, all individuals were divided into two groups： high level group and low level group, while all individuals were divided into two groups whether the level of LDL-C was achieve 2.06 mmol/L. We classified the participants into CAD group and non-CAD group on the basis of CAG. The incidence of CAD was compared between the two groups of four different lipid indicators. The ability of estimating CAD was described by Reciever Operating Characteristic curve （ROC curve）. Result There were significantly statistical differences in the incidence of CAD between the high level group and low level group of ApoB100/ApoA1 ratio （75.0% vs. 55.9%, %2 = 19.681, P 〈 0.001）. By logistic regression analysis, odds ratio of ApoB100/ApoA1 ratio was 2.142, 95% CI （1.437, 3.195）（P 〈 0.001）. The AUC （area under curve） of ApoB100/ApoA1 ratio were 0.66. There were significant for diagnosis of CAD （P 〈 0.001）. Conclusion The ApoB100/ApoA1 ratio was an independent risk factor of CAD in elderly population, and it is better than traditional lipid indicators, and can be used for the ability of estimating CAD.展开更多
氧化修饰低密度脂蛋白(oxidized low density lipoprotein,oxLDL)被认为是动脉硬化的关键致病因素。oxLDL的性能与其唯一的组成蛋白——载脂蛋白B-100(apoB-100)的二级结构即构象密切相关。荧光光谱和圆二色(CD)光谱是研究蛋白质构象的...氧化修饰低密度脂蛋白(oxidized low density lipoprotein,oxLDL)被认为是动脉硬化的关键致病因素。oxLDL的性能与其唯一的组成蛋白——载脂蛋白B-100(apoB-100)的二级结构即构象密切相关。荧光光谱和圆二色(CD)光谱是研究蛋白质构象的有力手段,因此在oxLDL结构的研究中也有广泛的应用。本文综述了近年来荧光光谱和圆二色光谱在LDL氧化研究方面的应用,并对今后的研究方向做了展望。展开更多
低密度脂蛋白(LDL)所含的色氨酸(Trp)、赖氨酸(Lys)发生氧化修饰是导致动脉粥样硬化(AS)形成的重要因素。为反映丁香乙酸乙酯相(EAFC)对LDL氧化过程中Trp、Lys修饰的抑制作用,本文首先对LDL氧化评价孵育体系中氧化剂Cu SO4及底物LDL浓...低密度脂蛋白(LDL)所含的色氨酸(Trp)、赖氨酸(Lys)发生氧化修饰是导致动脉粥样硬化(AS)形成的重要因素。为反映丁香乙酸乙酯相(EAFC)对LDL氧化过程中Trp、Lys修饰的抑制作用,本文首先对LDL氧化评价孵育体系中氧化剂Cu SO4及底物LDL浓度进行优化;进而以荧光为主要指标对这种抑制效果进行了评价。结果表明,选定CuSO_4浓度1.25、25μmol/L与LDL浓度500μg/m L为配比做后续实验。20μg/m L EAFC能抑制Trp降解导致的荧光淬灭,抑制作用显著高于1μg/m L阳性对照(2,6-二叔丁基对甲基苯酚,BHT)(p<0.01)。3μg/m L EAFC能抑制高反应活性醛修饰Lys,10μg/m L EAFC能显著抑制Lys与4-HNE共价结合(p<0.01)。15μg/m L EAFC能有效抑制Lys与MDA交联,抑制效果强于1μg/m L BHT。15μg/m L EAFC能显著抑制脂褐素形成(p<0.01)。本文为后期解析EAFC抑制LDL氧化修饰作用方式、抑制氧化LDL与清道夫受体之间识别等作用机理提供参考。展开更多
Vitellogenins(VITs),the lipoprotein precursors of yolk proteins in Caenorhabditis elegans,are expressed in the intestine,secreted into the pseudocoelom,and ultimately transported into oocytes.However,the mechanism by ...Vitellogenins(VITs),the lipoprotein precursors of yolk proteins in Caenorhabditis elegans,are expressed in the intestine,secreted into the pseudocoelom,and ultimately transported into oocytes.However,the mechanism by which VITs are secreted out of the intestine remains unclear.In this study,a candidate RNA interference(RNAi)screen suggested that both the conventional secretion pathway and recycling endosomes(REs)are essential for VIT secretion.In addition to expected conventional secretion,VITs were also found to be synthesized in the intestinal rough endoplasmic reticulum(ER)and then transported to the Golgi apparatus.VIT-2::GFP accumulated in enlarged REs upon depletion of receptor-mediated endocytosis 1(RME-1),a key protein that facilitates endocytic recycling.Moreover,the number of VIT-2::GFP-containing REs decreased upon inhibition of either ER-to-Golgi trafficking,trans-Golgi-to-endosome trafficking,or endocytosis.These findings suggested that REs are required for intestinal secretion of both newly synthesized VITs and yolk proteins endocytosed from the pseudocoelom.Moreover,RME-1 was found at the periphery of vitellogenin-containing vesicles(VVs),and this required RAB-10,the upstream regulator of RME-1 in endocytic recycling.RAB-10 was additionally required for the trafficking of VV from the apical/luminal side to the basal/pseudocoelomic side of the intestine.Together,these results identify REs as an intermediate compartment for the secretion of VIT/yolk proteins out of the intestine,suggesting a conserved role for endocytic recycling in the secretion of lipoproteins in mammals,particularly those assembled by apolipoprotein B-100(apoB-100),a mammalian homolog of VITs.展开更多
文摘动脉粥样硬化是由多种因素共同作用导致的血管壁的免疫炎症性疾病,是众多心血管疾病发生的主要病理基础。目前比较公认的动脉粥样硬化发生机制是"炎症反应"学说,即低密度脂蛋白(low density lipoprotein,LDL)中所包含的载脂蛋白ApoB-100的异常增高引起的病理性炎症反应是导致动脉粥样硬化的主要因素。通过免疫疗法抑制ApoB-100导致的病理性炎症反应,有望延缓动脉粥样硬化的发生与发展。该文主要围绕ApoB-100疫苗以及其他ApoB-100抑制剂的最新进展和存在的问题进行综述。
基金supported by 973 Program(No2007CB714506)NSFC(Nos20925517,21005019)+1 种基金STCSM(Nos 10XD1406000,09JC 1402600)Shanghai Leading Academic Discipline Project(NoB109)
文摘Apolipoprotein B100（apoB-100） is a major protein of the cholesterol-rich low-density lipoprotein（LDL） and reflects a better assessment of total atherogenic burden to the vascular system than LDL.In this work,a simple and sensitive method has been developed to determine picoliter apoB-100s using the PMMA microfluidic chip coupled with electrochemical detection system. This method performs very well with a detectable linear range of 1-800 pg/mL and a detection limit of 1 pg/mL.A real serum sample has further been detected by this microchip-based biosensor.The results show that this kind of method is practicable and has the potential application in clinical analysis and diagnosis.
基金supportet by the grants from The Science and Techonlogy Planning Project of Gungdong Prvince (2010B060900105) and (2011B061300034)
文摘Background Less studies were done to compare the lipid ratios including ApoB100/ApoA1, LDL-C/HDL- C,TC/HDL-Cin elderly. So the study was to investigate the relationship between Apolipoprotein B100/ApoA1 ratio and coronary artery disease （CAD） in elderly. Methods 498 participants aged over 65 years with chest pain had been subsumed from Sep. 2009 to April 2011 of Guangdong General Hospital. Clinic informations of gender, age, history of hypertension, diabetes mellitus, smoking was collected. Simultaneously, serum lipids should be phlebotomized in 24 hours after be inpatient. ApoB100/ApoA1 ratio, LDL-C/HDL-C ratio. TC/HDL-C ratio, non-HDL-C were calculated using the above data. Accroding to the mean of ApoB100/ApoA1 ratio, ApoB100, non-HDL-C, all individuals were divided into two groups： high level group and low level group, while all individuals were divided into two groups whether the level of LDL-C was achieve 2.06 mmol/L. We classified the participants into CAD group and non-CAD group on the basis of CAG. The incidence of CAD was compared between the two groups of four different lipid indicators. The ability of estimating CAD was described by Reciever Operating Characteristic curve （ROC curve）. Result There were significantly statistical differences in the incidence of CAD between the high level group and low level group of ApoB100/ApoA1 ratio （75.0% vs. 55.9%, %2 = 19.681, P 〈 0.001）. By logistic regression analysis, odds ratio of ApoB100/ApoA1 ratio was 2.142, 95% CI （1.437, 3.195）（P 〈 0.001）. The AUC （area under curve） of ApoB100/ApoA1 ratio were 0.66. There were significant for diagnosis of CAD （P 〈 0.001）. Conclusion The ApoB100/ApoA1 ratio was an independent risk factor of CAD in elderly population, and it is better than traditional lipid indicators, and can be used for the ability of estimating CAD.
文摘氧化修饰低密度脂蛋白(oxidized low density lipoprotein,oxLDL)被认为是动脉硬化的关键致病因素。oxLDL的性能与其唯一的组成蛋白——载脂蛋白B-100(apoB-100)的二级结构即构象密切相关。荧光光谱和圆二色(CD)光谱是研究蛋白质构象的有力手段,因此在oxLDL结构的研究中也有广泛的应用。本文综述了近年来荧光光谱和圆二色光谱在LDL氧化研究方面的应用,并对今后的研究方向做了展望。
文摘低密度脂蛋白(LDL)所含的色氨酸(Trp)、赖氨酸(Lys)发生氧化修饰是导致动脉粥样硬化(AS)形成的重要因素。为反映丁香乙酸乙酯相(EAFC)对LDL氧化过程中Trp、Lys修饰的抑制作用,本文首先对LDL氧化评价孵育体系中氧化剂Cu SO4及底物LDL浓度进行优化;进而以荧光为主要指标对这种抑制效果进行了评价。结果表明,选定CuSO_4浓度1.25、25μmol/L与LDL浓度500μg/m L为配比做后续实验。20μg/m L EAFC能抑制Trp降解导致的荧光淬灭,抑制作用显著高于1μg/m L阳性对照(2,6-二叔丁基对甲基苯酚,BHT)(p<0.01)。3μg/m L EAFC能抑制高反应活性醛修饰Lys,10μg/m L EAFC能显著抑制Lys与4-HNE共价结合(p<0.01)。15μg/m L EAFC能有效抑制Lys与MDA交联,抑制效果强于1μg/m L BHT。15μg/m L EAFC能显著抑制脂褐素形成(p<0.01)。本文为后期解析EAFC抑制LDL氧化修饰作用方式、抑制氧化LDL与清道夫受体之间识别等作用机理提供参考。
基金supported by the National Institutes of Health Office of Infrastructure Programs(P40 OD010440),for providing the wild-type N2 strainfunded by the National Natural Science Foundation of China(NSFC-ISF 32061143020 to M.Q.D.),the Ministry of Science and Technology of the People’s Republic of China(institutional grants to NIBS,Beijing,a fund of the National High-Level Talents Special Support Program to M.Q.D.)the Beijing Municipal Science and Technology Commission(institutional grants to NIBS,Beijing and a fund for cultivation and development of innovation base to M.Q.D.).
文摘Vitellogenins(VITs),the lipoprotein precursors of yolk proteins in Caenorhabditis elegans,are expressed in the intestine,secreted into the pseudocoelom,and ultimately transported into oocytes.However,the mechanism by which VITs are secreted out of the intestine remains unclear.In this study,a candidate RNA interference(RNAi)screen suggested that both the conventional secretion pathway and recycling endosomes(REs)are essential for VIT secretion.In addition to expected conventional secretion,VITs were also found to be synthesized in the intestinal rough endoplasmic reticulum(ER)and then transported to the Golgi apparatus.VIT-2::GFP accumulated in enlarged REs upon depletion of receptor-mediated endocytosis 1(RME-1),a key protein that facilitates endocytic recycling.Moreover,the number of VIT-2::GFP-containing REs decreased upon inhibition of either ER-to-Golgi trafficking,trans-Golgi-to-endosome trafficking,or endocytosis.These findings suggested that REs are required for intestinal secretion of both newly synthesized VITs and yolk proteins endocytosed from the pseudocoelom.Moreover,RME-1 was found at the periphery of vitellogenin-containing vesicles(VVs),and this required RAB-10,the upstream regulator of RME-1 in endocytic recycling.RAB-10 was additionally required for the trafficking of VV from the apical/luminal side to the basal/pseudocoelomic side of the intestine.Together,these results identify REs as an intermediate compartment for the secretion of VIT/yolk proteins out of the intestine,suggesting a conserved role for endocytic recycling in the secretion of lipoproteins in mammals,particularly those assembled by apolipoprotein B-100(apoB-100),a mammalian homolog of VITs.
