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Comparative Structures and Evolution of Vertebrate Carboxyl Ester Lipase (CEL) Genes and Proteins with a Major Role in Reverse Cholesterol Transport. 在逆向胆固醇转运中起主要作用的脊椎动物羧基酯脂肪酶(CEL)基因和蛋白质的比较结构和进化。
Pub Date : 2011-01-01 Epub Date: 2011-11-21 DOI: 10.1155/2011/781643
Roger S Holmes, Laura A Cox

Bile-salt activated carboxylic ester lipase (CEL) is a major triglyceride, cholesterol ester and vitamin ester hydrolytic enzyme contained within pancreatic and lactating mammary gland secretions. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures and gene locations for CEL genes, and encoded proteins using data from several vertebrate genome projects. A proline-rich and O-glycosylated 11-amino acid C-terminal repeat sequence (VNTR) previously reported for human and other higher primate CEL proteins was also observed for other eutherian mammalian CEL sequences examined. In contrast, opossum CEL contained a single C-terminal copy of this sequence whereas CEL proteins from platypus, chicken, lizard, frog and several fish species lacked the VNTR sequence. Vertebrate CEL genes contained 11 coding exons. Evidence is presented for tandem duplicated CEL genes for the zebrafish genome. Vertebrate CEL protein subunits shared 53-97% sequence identities; demonstrated sequence alignments and identities for key CEL amino acid residues; and conservation of predicted secondary and tertiary structures with those previously reported for human CEL. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the vertebrate CEL family of genes which were related to a nematode carboxylesterase (CES) gene and five mammalian CES gene families.

胆盐活化羧酸酯脂肪酶(CEL)是存在于胰腺和哺乳期乳腺分泌物中的一种主要的甘油三酯、胆固醇酯和维生素酯水解酶。利用生物信息学方法预测CEL基因的氨基酸序列、二级和三级结构和基因位置,并利用多个脊椎动物基因组计划的数据编码蛋白质。先前报道的富含脯氨酸和o -糖基化的11氨基酸c末端重复序列(VNTR)在人类和其他高等灵长类动物的CEL蛋白中也被观察到。相比之下,负鼠的CEL含有该序列的单个c端拷贝,而鸭嘴兽、鸡、蜥蜴、青蛙和几种鱼类的CEL蛋白则缺乏VNTR序列。脊椎动物细胞基因包含11个编码外显子。证据提出串联重复CEL基因斑马鱼基因组。脊椎动物细胞蛋白亚基具有53-97%的序列一致性;证明了关键CEL氨基酸残基的序列比对和身份;预测的二级和三级结构与先前报道的人类CEL的保守性。系统发育分析证实了与线虫羧酸酯酶(CES)基因和5个哺乳动物CES基因家族相关的脊椎动物CEL基因家族的关系和潜在的进化起源。
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引用次数: 25
The Effects of Very-Low-Calorie Diets on HDL: A Review. 极低热量饮食对高密度脂蛋白的影响:综述
Pub Date : 2011-01-01 Epub Date: 2010-12-22 DOI: 10.1155/2011/306278
Catherine Rolland, Iain Broom

This paper investigates the effects of very-low-calorie diets (VLCDs) used in the treatment of obesity on high-density lipoprotein (HDL) levels. Although the studies varied widely in their intervention format, duration, and baseline HDL levels, it would appear that HDL levels usually decrease during active weight loss using a VLCD, but these either return to pre-VLCD levels or improve overall during the weight-maintenance phase. More research needs to be done to determine optimal weight-maintenance programmes and the effects of VLCDs in the short term as well as on HDL levels in groups at increased risk of coronary heart disease.

本文研究了极低热量饮食(vlcd)对肥胖治疗中高密度脂蛋白(HDL)水平的影响。尽管这些研究在干预形式、持续时间和基线HDL水平上差异很大,但似乎在使用VLCD的积极减肥期间,HDL水平通常会下降,但在体重维持阶段,这些水平要么恢复到VLCD前的水平,要么总体上有所改善。需要做更多的研究来确定最佳的体重维持方案和vlcd在短期内的影响,以及对冠心病风险增加人群中高密度脂蛋白水平的影响。
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引用次数: 18
Prevalence of dyslipidemia in patients receiving health checkups: a hospital-based study. 接受健康检查的患者中血脂异常的患病率:一项基于医院的研究
Pub Date : 2011-01-01 Epub Date: 2011-10-26 DOI: 10.1155/2011/314234
Kao-Chi Cheng, Yu-Lung Chen, Shih-Wei Lai

We used the dataset from one medical center in Taiwan to explore the prevalence of dyslipidemia, which included 2695 subjects receiving private health checkups in 2003-2004. The overall prevalence of hypercholesterolemia was 53.3% in men and 48.2% in women (P = 0.008). The overall prevalence of hypertriglyceridemia was 29.3% in men and 13.7% in women (P < 0.001). The overall prevalence of elevated LDL level was 50.7% in men and 37.9% in women (P < 0.001). The overall prevalence of low HDL level was 47.4% in men and 53% in women (P = 0.004).

我们使用台湾某医疗中心的资料集,探讨血脂异常的流行情况,其中包括2003-2004年间接受私人健康检查的2695名受试者。高胆固醇血症的总体患病率男性为53.3%,女性为48.2% (P = 0.008)。高甘油三酯血症的总体患病率男性为29.3%,女性为13.7% (P < 0.001)。LDL水平升高的总体患病率男性为50.7%,女性为37.9% (P < 0.001)。低HDL水平的总体患病率男性为47.4%,女性为53% (P = 0.004)。
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引用次数: 5
Prevalence of metabolic syndrome in urban India. 印度城市代谢综合征的患病率。
Pub Date : 2011-01-01 Epub Date: 2011-05-19 DOI: 10.1155/2011/920983
Apurva Sawant, Ranjit Mankeshwar, Swarup Shah, Rani Raghavan, Gargi Dhongde, Himanshu Raje, Shoba D'souza, Aarti Subramanium, Pradnya Dhairyawan, Seema Todur, Tester F Ashavaid

Background. Metabolic syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. Materials and Methods. The current study was a population-based survey of cohort of subjects in the metropolitan city of Mumbai. A total of 548 subjects, who attended the CARDIAC evaluation camp, were recruited in the study. Participants with complete fasting lipid profiles, blood glucose, and known cardiac risk markers were evaluated. Results. On applying modified NCEP ATP III, we found out that nearly 95% of the subjects had at least one abnormal parameter. We found the prevalence of MS in our study population to be 19.52%. The prevalence of MS in males was almost double than females (P = .008). The overall prevalence of BMI (>23 kg/m(2)) was 79.01%. Increased hypertriglyceridemia and decreased levels of HDL-C were found to be more in males (P < .0001). Conclusion. The low percentage of subjects with normal and controlled parameters suggests that there is a need for awareness programs and lifestyle interventions for the prevention and control of MS.

背景。代谢综合征(MS)的特点是心血管疾病的个体危险因素的星座。材料与方法。目前的研究是一项以人口为基础的调查,研究对象是孟买大城市的一群人。本研究共招募了548名参加心脏评估营的受试者。对空腹血脂、血糖和已知心脏危险指标完整的参与者进行评估。结果。应用改进的NCEP ATP III,我们发现近95%的受试者至少有一个参数异常。我们发现MS在我们的研究人群中的患病率为19.52%。男性MS患病率几乎是女性的两倍(P = 0.008)。BMI (>23 kg/m(2))的总患病率为79.01%。高甘油三酯血症的增加和HDL-C水平的降低在男性中更为明显(P < 0.0001)。结论。正常和控制参数的受试者比例较低,这表明有必要进行意识规划和生活方式干预,以预防和控制MS。
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引用次数: 137
The role of high-density lipoproteins in reducing the risk of vascular diseases, neurogenerative disorders, and cancer. 高密度脂蛋白在降低血管疾病、神经变性疾病和癌症风险方面的作用。
Pub Date : 2011-01-01 Epub Date: 2010-12-23 DOI: 10.1155/2011/496925
Donovan McGrowder, Cliff Riley, Errol Y St A Morrison, Lorenzo Gordon

High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including "healthy" diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

高密度脂蛋白(HDL)是血液中胆固醇的主要载体之一。它之所以受到特别关注,是因为与其他脂蛋白相比,除非高密度脂蛋白发生病理性改变,否则高密度脂蛋白的许多生理功能都会对心血管系统产生有利影响。最近引起关注的高密度脂蛋白功能包括抗炎和抗氧化活性。高密度脂蛋白的高抗氧化和抗炎活性与保护心血管疾病有关。动脉粥样硬化保护活性以及高密度脂蛋白的功能缺陷最终取决于高密度脂蛋白的蛋白质和脂质组成。此外,大量流行病学研究表明,高密度脂蛋白胆固醇与认知障碍之间存在保护性联系。氧化应激,包括脂质过氧化,已被证明是阿尔茨海默病众多风险因素病理效应的介质。经证实,能提高高密度脂蛋白胆固醇水平的生活方式干预措施(包括 "健康 "饮食、定期锻炼、控制体重和戒烟)也具有保护神经的作用。本综述将重点介绍高密度脂蛋白胆固醇对心血管疾病、乳腺癌和肺癌、非霍奇金淋巴瘤的有益作用,以及其在降低阿尔茨海默病和痴呆症风险方面的神经保护潜力。
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引用次数: 0
Methotrexate in atherogenesis and cholesterol metabolism. 甲氨蝶呤在动脉粥样硬化和胆固醇代谢中的作用。
Pub Date : 2011-01-01 Epub Date: 2011-02-22 DOI: 10.1155/2011/503028
Eric Coomes, Edwin S L Chan, Allison B Reiss

Methotrexate is a disease-modifying antirheumatic drug commonly used to treat inflammatory conditions such as rheumatoid arthritis which itself is linked to increased cardiovascular risk. Treatments that target inflammation may also impact the cardiovascular system. While methotrexate improves cardiovascular risk, inhibition of the cyclooxygenase (COX)-2 enzyme promotes atherosclerosis. These opposing cardiovascular influences may arise from differing effects on the expression of proteins involved in cholesterol homeostasis. These proteins, ATP-binding cassette transporter (ABC) A1 and cholesterol 27-hydroxylase, facilitate cellular cholesterol efflux and defend against cholesterol overload. Methotrexate upregulates expression of cholesterol 27-hydroxylase and ABCA1 via adenosine release, while COX-2 inhibition downregulates these proteins. Adenosine, acting through the A(2A) and A(3) receptors, may upregulate proteins involved in reverse cholesterol transport by cAMP-PKA-CREB activation and STAT inhibition, respectively. Elucidating underlying cardiovascular mechanisms of these drugs provides a framework for developing novel cardioprotective anti-inflammatory medications, such as selective A(2A) receptor agonists.

甲氨蝶呤是一种改善疾病的抗风湿药物,通常用于治疗炎症性疾病,如类风湿关节炎,它本身与心血管风险增加有关。针对炎症的治疗也可能影响心血管系统。虽然甲氨蝶呤可以提高心血管风险,但抑制环氧化酶(COX)-2酶会促进动脉粥样硬化。这些相反的心血管影响可能源于对参与胆固醇稳态的蛋白质表达的不同影响。这些蛋白,atp结合盒转运蛋白(ABC) A1和胆固醇27-羟化酶,促进细胞胆固醇外泄和防御胆固醇过载。甲氨蝶呤通过腺苷释放上调胆固醇27-羟化酶和ABCA1的表达,而抑制COX-2则下调这些蛋白的表达。腺苷通过A(2A)和A(3)受体作用,可能分别通过cAMP-PKA-CREB激活和STAT抑制上调参与逆向胆固醇转运的蛋白。阐明这些药物潜在的心血管机制为开发新的心脏保护抗炎药物提供了框架,如选择性a (2A)受体激动剂。
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引用次数: 55
The Fruit Fly Drosophila melanogaster as a Model System to Study Cholesterol Metabolism and Homeostasis. 果蝇黑腹果蝇作为研究胆固醇代谢和体内平衡的模型系统。
Pub Date : 2011-01-01 Epub Date: 2011-01-20 DOI: 10.1155/2011/176802
Ryusuke Niwa, Yuko S Niwa

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC) disease genes, and DHR96.

胆固醇在影响细胞膜的生物物理特性和作为类固醇激素的前体方面的多种作用早已被认识到。虽然人们对胆固醇生物合成的许多方面都很了解,但目前对胆固醇代谢和体内平衡的分子机制知之甚少。最近,遗传方法在果蝇,黑腹果蝇,已经成功地用于分析调节胆固醇代谢和体内平衡的分子机制。本文综述了近年来有关调节胆固醇代谢和体内平衡的基因的研究进展,包括neverland、Niemann Pick type C(NPC)病基因和DHR96。
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引用次数: 63
Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens. 通过抑制蛋鸡肝脏胆固醇合成和促进胆汁酸合成,膳食中的卡拉亚皂苷和荚膜罗氏菌具有降胆固醇作用
Pub Date : 2010-01-01 Epub Date: 2010-06-30 DOI: 10.1155/2010/272731
Sadia Afrose, Md Sharoare Hossain, Ummay Salma, Abdul Gaffar Miah, Hirotada Tsujii

This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of (14)C from 1-(14)C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver.

本研究旨在阐明卡拉亚皂苷或罗氏杆菌(R. capsulatus)降血脂作用的机制。研究人员将 40 只蛋鸡(20 周龄)分成 4 个日粮处理组,分别饲喂基础日粮(对照组)或添加卡拉亚皂苷、荚膜杆菌或两者的基础日粮 60 天。所有添加剂都降低了血清低密度脂蛋白胆固醇水平以及血清、肝脏和蛋黄中胆固醇和甘油三酯的水平(P < .05)。补充卡拉亚皂苷、蒴果莓以及卡拉亚皂苷和蒴果莓的组合可同时提高肝脏胆汁酸浓度和粪便中胆固醇、三酰甘油和胆汁酸的浓度(P < .05)。补充卡拉亚皂苷、蒴果莓以及卡拉亚皂苷和蒴果莓的组合能抑制肝脏体外总脂、磷脂、三酰甘油和胆固醇组分中 1-(14)C 棕榈酸的 (14)C 结合(P < .05)。这些研究结果表明,卡拉亚皂苷和蒴果莓的降胆固醇作用是通过抑制肝脏中胆固醇的合成和促进胆固醇的分解代谢而产生的。
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引用次数: 0
Randomized Trial of a Pharmacist-Delivered Intervention for Improving Lipid-Lowering Medication Adherence among Patients with Coronary Heart Disease. 一项药剂师介入改善冠心病患者降脂药物依从性的随机试验
Pub Date : 2010-01-01 Epub Date: 2010-08-17 DOI: 10.1155/2010/383281
Yunsheng Ma, Ira S Ockene, Milagros C Rosal, Philip A Merriam, Judith K Ockene, Pritesh J Gandhi

A randomized trial of a pharmacist-delivered intervention (PI) versus usual care (UC) was conducted; 689 subjects with known coronary heart disease were recruited from cardiac catheterization laboratories. Participants in the PI condition received 5 pharmacist-delivered telephone counseling calls post-hospital discharge. At one year, 65% in the PI condition and 60% in the UC condition achieved an LDL-C level <100 mg/dL (P = .29); mean statin adherence was 0.88 in the PI, and 0.90 in the UC (P = .51). The highest percentage of those who reached the LDL-C goal were participants who used statins as opposed to those who did not use statins (67% versus 58%, P = .05). However, only 53% and 56% of the patients in the UC and PI conditions, respectively, were using statins. We conclude that a pharmacist-delivered intervention aimed only at improving patient adherence is unlikely to positively affect outcomes. Efforts must be oriented towards influencing physicians to increase statin prescription rates.

进行了一项药剂师提供的干预(PI)与常规护理(UC)的随机试验;从心导管实验室招募了689名已知冠心病患者。PI状态的参与者在出院后接受了5次药剂师提供的电话咨询电话。一年后,65%的PI组和60%的UC组达到了LDL-C水平
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引用次数: 36
Influence of soy lecithin administration on hypercholesterolemia. 服用大豆卵磷脂对高胆固醇血症的影响
Pub Date : 2010-01-01 Epub Date: 2009-12-28 DOI: 10.1155/2010/824813
Amouni Mohamed Mourad, Eder de Carvalho Pincinato, Priscila Gava Mazzola, Maricene Sabha, Patricia Moriel

Recent studies suggest that lecithin-rich diet can modify cholesterol homeostasis and hepatic lipoprotein metabolism. Considering the phytotherapeutic impact of lecithin, this work hypothesizes that lecithin administration in hypercholesterolemic patients may reduce cholesterol concentrations by increasing biliary secretion. Total cholesterol and LDL were evaluated after soy lecithin administration in hypercholesterolemic patients. One soy lecithin capsule (500 mg/RP-Sherer) was administrated daily. One-two months before the treatment beginning, blood samples were collected for total lipids and cholesterol fractions analysis. The results showed a reduction of 40.66% and 42.00% in total cholesterol and of 42.05% and 56.15% in LDL cholesterol after treatment for one and two months, respectively. A significant reduction in total cholesterol and LDL-cholesterol concentrations was observed during the first month of treatment, suggesting that the administration of soy lecithin daily may be used as a supplemental treatment in hypercholesterolemia.

最近的研究表明,富含卵磷脂的饮食可改变胆固醇稳态和肝脏脂蛋白代谢。考虑到卵磷脂的植物治疗作用,本研究假设高胆固醇血症患者服用卵磷脂可通过增加胆汁分泌来降低胆固醇浓度。对高胆固醇血症患者服用大豆卵磷脂后的总胆固醇和低密度脂蛋白进行了评估。每天服用一粒大豆卵磷脂胶囊(500 毫克/粒-舍勒)。治疗开始前 12 个月,采集血液样本进行总血脂和胆固醇组分分析。结果显示,治疗一个月和两个月后,总胆固醇分别降低了 40.66% 和 42.00%,低密度脂蛋白胆固醇分别降低了 42.05% 和 56.15%。在治疗的第一个月,总胆固醇和低密度脂蛋白胆固醇的浓度明显降低,这表明每天服用大豆卵磷脂可作为高胆固醇血症的辅助治疗。
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引用次数: 0
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