共查询到17条相似文献，搜索用时 46 毫秒
1.
血浆高密度脂蛋白(HDL)与低密度脂蛋白(LDL)一样可以在体内外发生氧化修饰,引起其理化性质发生一系列的改变,如多不饱和脂肪酸过氧化,卵磷脂水解,蛋白质发生聚合或分解等.活体内HDL可能在动脉壁巨噬细胞、内皮细胞及中性粒细胞、单核细胞的作用下发生氧化修饰.氧化修饰HDL可能通过清道夫受体途径代谢.氧化修饰HDL产生多种致动脉粥样硬化作用.维生素E、C的摄入可能有助于防止脂蛋白的氧化. 相似文献
2.
高密度脂蛋白抗动脉粥样硬化作用 总被引：1，自引：0，他引：1
高密度脂蛋白通过清道夫受体BI(SR—BI)选择性的摄取外周组织细胞胆固酵,调节胆固酵逆转运过程;依赖对氧磷酶-1(PON1)的抗氧化作用及过氧化体增殖物激活型受体(PPAR-α)调节HDL代谢过程中5种蛋白质编码基因的表达等多种机制发挥其抗AS作用。 相似文献
3.
高胆固醇饲料喂养造成的动脉粥样硬化(As)模型家兔通过静脉注射人血浆HDL制剂,观察HDL对As家兔肝细胞膜LDL受体活性的影响.结果发现,摄取高胆固醇饲料的As家兔,其肝细胞膜LDL受体Kd值虽无明显变化但Bmax值显著减小（P＜0.01,与正常对照组比较);注射HDL制剂后,As家兔肝细胞膜LDL受体Kd值仍无明显改变,但Bmax值却显著回升（P＜0.01,与高脂组比较).表明人血浆HDL具有增加As家兔肝细胞膜LDL受体活性的作用. 相似文献
4.
高胆固醇饲料喂养造成的动脉粥样硬化（Ａｓ） 模型家兔通过静脉注射人血浆ＨＤＬ 制剂, 观察ＨＤＬ 对Ａｓ家兔肝细胞膜ＬＤＬ受体活性的影响． 结果发现, 摄取高胆固醇饲料的Ａｓ 家兔, 其肝细胞膜ＬＤＬ 受体 Ｋｄ 值虽无明显变化但Ｂｍａｘ 值显著减小（ Ｐ＜ ０－０１ , 与正常对照组比较） ; 注射ＨＤＬ 制剂后, Ａｓ 家兔肝细胞膜ＬＤＬ受体Ｋｄ 值仍无明显改变, 但Ｂｍａｘ 值却显著回升（ Ｐ＜ ０－０１ , 与高脂组比较） ． 表明人血浆ＨＤＬ 具有增加Ａｓ 家兔肝细胞膜ＬＤＬ 受体活性的作用． 相似文献
5.
载脂蛋白A-I抗动脉粥样硬化的研究进展 总被引：3，自引：0，他引：3
载脂蛋白A—I是HDL最主要的结构成分,是卵磷脂胆固醇酰基转移酶的主要激活剂。它决定了HDL的代谢和在血浆中的浓度。实验已经证明,载脂蛋白A—I具有抗动脉粥样硬化症的功能。在这里阐述了载脂蛋白A—I的结构和制备;载脂蛋白A—I和HDL的关系以及它在抗动脉粥样硬化方面的作用和可能的机理：胆固醇的逆向转运、抗氧化作用和调节炎症反应。 相似文献
6.
高密度脂蛋白受体(SR-BI)和胆固醇逆转运 总被引：1，自引：0，他引：1
近十几年来对小鼠的B类I型清道夫受体(SRBI)的研究,发现它是一种高亲和力的高密度脂蛋白受体,主要在肝脏和类固醇源性组织中表达。该受体能介导胆固醇酯的选择性吸收,在高密度脂蛋白(HDL)的代谢和胆固醇的“逆转运”中起重要作用。动物实验证明SRBI的表达可减少动脉粥样硬化的发生。如果SRBI对人有相似的作用,它将成为一个好的作用靶点用于临床心脑血管疾病的治疗 。 相似文献
7.
胆固醇逆向转运(reverse cholesterol transport,RCT)是促进外周胆固醇从细胞内流出,然后转运到肝脏进行代谢的过程,是机体抗动脉粥样硬化相关疾病的重要机制。研究表明,感染、炎症及创伤等诱导的急性期应答(acute phase response,APR)影响高密度脂蛋白的结构和功能,抑制细胞内胆固醇流出、血浆胆固醇转运及肝脏胆固醇代谢和排泌等环节,因此抑制体内RCT。APR短期抑制RCT有利于机体抗感染和组织损伤,然而,APR对RCT的进一步抑制将促进外周组织胆固醇蓄积及代谢紊乱,可能是多种感染免疫性疾病、代谢性疾病与动脉粥样硬化呈正相关的关键因素。本文就APR调节机体RCT的最新研究进展作一综述。 相似文献
8.
血浆载脂蛋白A-Ⅰ(apoA-Ⅰ)的水平与动脉粥样硬化(atherosclerosis,AS)性心血管疾病的风险呈负相关.ApoA-Ⅰ经载脂形成高密度脂蛋白(HDL),HDL通过促进胆固醇逆向转运(RCT),使细胞内的多余胆固醇流出.α螺旋是apoA-Ⅰ载脂的主要结构,在apoA-Ⅰ参与的胆固醇流出中具有重要作用.模拟α螺旋建立的apoA-Ⅰ模拟肽能通过不同方式发挥抗AS的作用.本文就α螺旋在胆固醇流出中的作用作一综述,以便进一步探索apoA-Ⅰ的结构对胆固醇流出的影响,为以apoA-Ⅰ为靶点防治AS提供理论基础. 相似文献
9.
高密度脂蛋白（high density lipoprotein,HDL）血浆水平与动脉粥样硬化（atherosclerosis,AS）性心血管疾病呈负相关,成为抗AS的重要靶点和热点.然而,近年来多个临床试验未能证明升高血浆HDL的水平对心血管的保护作用,使得人们开始重新审视HDL抗AS功能生物学特性的复杂性.近5年来的研究发现,HDL可通过对造血干细胞（hematopoietic stem cells,HSCs）和内皮祖细胞（endothelial progenitor cells,EPCs）功能的调节发挥抗AS 的作用,本文就这一新机制进行综述,期待为HDL迄今尚不完全清楚的复杂心血管保护机制提供研究思路. 相似文献
10.
研究已经证实血浆高密度脂蛋白胆固醇(HDL-C)水平与冠状动脉疾病(CAD)的发生呈负相关,因此,HDL-C水平的调控成为CAD治疗的研究热点.HDL水平高低与其自身的产生和代谢密切相关,而HDL的产生和代谢主要由相应的调控基因决定,有研究表明,血浆HDL-C水平具有显著的遗传基础,遗传率达到40%～60%,提示研究影响HDL-C水平的遗传性因素具有重要意义.候选基因、全基因组连锁以及近来的全基因组关联(GWA)研究已鉴定出影响血浆HDL-C水平的多种遗传变异,但这些遗传变异并不都与CAD相关,对于其功能性作用还未阐明.本文将分别对HDL的结构、产生和代谢,以及HDL-C水平相关的遗传性因素进行总结,并着重结合候选基因分析以及近来GWA研究的遗传学发现,阐述造成HDL-C水平变化的重要因子.提示运用综合性方法研究影响HDL-C水平的遗传性因素对于阐明HDL-C与CAD的关系,揭示CAD治疗新途径具有重要意义. 相似文献
11.
Genetic analysis of murine strains C57BL/6J and C3H/HeJ to confirm the map position ofAth-1, a gene determining atherosclerosis susceptibility 总被引：4，自引：0，他引：4
Beverly Paigen Deborah Albee Patricia A. Holmes Diane Mitchell 《Biochemical genetics》1987,25(7-8):501-511
Previous results suggested that strains C57BL/6J and C3H/HeJ differed in a single gene for atherosclerosis susceptibility, calledAth-1. Based on data from recombinant inbred strainsAth-1 was tentatively assigned to chromosome 1 linked toAlp-2. In this report, a cross between C57BL/6 and C3H/HeJ was carried out in order to test whether the tentative map position was correct. Parental strains and F1 and F2 progeny were examined. Susceptible alleles ofAth-1, found in C57BL/6, are associated with relatively low levels of high-density lipoprotein (HDL)-cholesterol in animals fed an atherogenic diet; resistant alleles ofAth-1 are associated with relatively high levels of HDL-cholesterol. F1 progeny have HDL levels that are intermediate between these of the two parental strains. Among the F2 progeny,Alp-2 andAth-1 cosegregated, providing confirmatory evidence thatAth-1 is linked toAlp-2 on chromosome 1. Three mice recombinant forAlp-2 andAth-1 were found among the 60 chromosomes tested, giving an estimated map distance between these two genes of 5.0±2.8 (SE) cM. The phenotypic characteristics ofAth-1 resemble a genetic trait in humans, hyperalphalipoproteinemia, which is characterized by elevated levels of HDL-cholesterol, reduced risk of heart disease, and increased longevity.This work was supported by Grant HL-32087 from the Heart, Lung, and Blood Institute, National Institutes of Health, Grant 1858 from the Council for Tobacco Research, Grant 86-1387 from the American Heart Association with funds contributed in part by the Alameda, Orange, and Santa Barbara County Chapters, and Grants 85-N132A and 85-N136A from the California Affiliate of the American Heart Association. 相似文献
12.
Troutt JS Alborn WE Mosior MK Dai J Murphy AT Beyer TP Zhang Y Cao G Konrad RJ 《Journal of lipid research》2008,49(3):581-587
Prebeta1 HDL is the initial plasma acceptor of cell-derived cholesterol in reverse cholesterol transport. Recently, small amphipathic peptides composed of D-amino acids have been shown to mimic apolipoprotein A-I (apoA-I) as a precursor for HDL formation. ApoA-I mimetic peptides have been proposed to stimulate the formation of prebeta1 HDL and increase reverse cholesterol transport in apoE-null mice. The existence of a monoclonal antibody (MAb 55201) and a corresponding ELISA method that is selective for the detection of the prebeta(1) subclass of HDL provides a means of establishing a correlation between apoA-I mimetic dose and prebeta1 HDL formation in human plasma. Using this prebeta1 HDL ELISA, we demonstrate marked apoA-I mimetic dose-dependent prebeta1 HDL formation in human plasma. These results correlated with increases in band density of the plasma prebeta1 HDL, when observed by Western blotting, as a function of increased apoA-I mimetic concentration. Increased prebeta1 HDL formation was observed after as little as 1 min and was maximal within 1 h. Together, these data suggest that a high-throughput prebeta1 HDL ELISA provides a way to quantitatively measure a key component of the reverse cholesterol transport pathway in human plasma, thus providing a possible method for the identification of apoA-I mimetic molecules. 相似文献
13.
Markku Ahotupa 《Free radical research》2017,51(4):439-447
Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD. 相似文献
14.
Nakanishi S Vikstedt R Söderlund S Lee-Rueckert M Hiukka A Ehnholm C Muilu M Metso J Naukkarinen J Palotie L Kovanen PT Jauhiainen M Taskinen MR 《Journal of lipid research》2009,50(2):183-192
The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL < or =10(th) and HDL > or =90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [(3)H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL(2), and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL(2), and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P < 0.0001), and the percentage of apoA-I present in the form of prebeta-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects. 相似文献
15.
Mireia Junyent Katherine L. Tucker Caren E. Smith Antonio Garcia-Rios Josiemer Mattei Chao-Qiang Lai Laurence D. Parnell Jose M. Ordovas 《Journal of lipid research》2009,50(3):565-573
Low HDL-cholesterol (HDL-C) is associated with an increased risk for atherosclerosis, and concentrations are modulated by genetic factors and environmental factors such as smoking. Our objective was to assess whether the association of common single-nucleotide polymorphisms (SNPs) at ABCG5/G8 (i18429G>A, i7892T>C, Gln604GluC>G, 5U145A>C, Tyr54CysA>G, Asp19HisG>C, i14222A>G, and Thr400LysC>A) genes with HDL-C differs according to smoking habit. ABCG5/G8 SNPs were genotyped in 845 participants (243 men and 602 women). ABCG5/G8 (i7892T>C, 5U145A>C, Tyr54CysA>G, Thr400LysC>A) SNPs were significantly associated with HDL-C concentrations (P < 0.001–0.013) by which carriers of the minor alleles at the aforementioned polymorphisms and homozygotes for the Thr400 allele displayed lower HDL-C. A significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5/G8 (Gln604GluC>G, Asp19HisG>C, i14222A>G) SNPs displayed lower concentrations of HDL-C only if they were smokers (P = 0.001–0.025). Also, for ABCG8_Thr400LysC>A SNP, smokers, but not nonsmokers, homozygous for the Thr400 allele displayed lower HDL-C (P = 0.004). Further analyses supported a significant haplotype global effect on lowering HDL-C (P = 0.002) among smokers. In conclusion, ABCG5/G8 genetic variants modulate HDL-C concentrations, leading to an HDL-C-lowering effect and thereby a potential increased risk for atherosclerosis only in smokers. 相似文献
16.
过多的胆固醇沉积在动脉壁对机体极为有害,可以引起动脉粥样硬化甚至心血管疾病.而胆固醇逆转运(reverse cholesterol transport,RCT)可以逆转此过程.传统的RCT是指胆固醇由外周组织转运回肝脏进行再循环或以胆汁酸的形式随粪便排出体外的过程,此过程受多种因子调控.近几年研究发现,胆固醇还可由血经过肠道直接分泌（transintestinal cholesterol efflux, TICE）通路随粪便排出体外,此过程对外界刺激更敏感.RCT已经成为防治动脉粥样硬化研究的新靶点,TICE有可能成为更有效的RCT调控通路. 相似文献
17.
A fraction of plasma transthyretin (TTR) circulates in HDL through binding to apolipoprotein A-I (apoA-I). Moreover, TTR is able to cleave the C terminus of lipid-free apoA-I. In this study, we addressed the relevance of apoA-I cleavage by TTR in lipoprotein metabolism and in the formation of apoA-I amyloid fibrils. We determined that TTR may also cleave lipidated apoA-I, with cleavage being more effective in the lipid-poor prebeta-HDL subpopulation. Upon TTR cleavage, discoidal HDL particles displayed a reduced capacity to promote cholesterol efflux from cholesterol-loaded THP-1 macrophages. In similar assays, TTR-containing HDL from mice expressing human TTR in a TTR knockout background had a decreased ability to perform reverse cholesterol transport compared with similar particles from TTR knockout mice, reinforcing the notion that cleavage by TTR reduces the ability of apoA-I to promote cholesterol efflux. As amyloid deposits composed of N-terminal apoA-I fragments are common in the atherosclerotic intima, we assessed the impact of TTR cleavage on apoA-I aggregation and fibrillar growth. We determined that TTR-cleaved apoA-I has a high propensity to form aggregated particles and that it formed fibrils faster than full-length apoA-I, as assessed by electron microscopy. Our results show that apoA-I cleavage by TTR may affect HDL biology and the development of atherosclerosis by reducing cholesterol efflux and increasing the apoA-I amyloidogenic potential. 相似文献