高密度脂蛋白亚型抗动脉粥样硬化血栓形成的作用机制

高密度脂蛋白胆固醇浓度与冠状动脉粥样硬化发生的危险性呈负相关。血浆高密度脂蛋白是一类颗粒大小不均一的脂蛋白,可分为两个大的亚型,即体大质轻的高密度脂蛋白2和小而密的高密度脂蛋白3。高密度脂蛋白及其载脂蛋白参与抗动脉粥样硬化可能涉及到的机制有:促胆固醇转运,维持内皮完整性,抑制血细胞粘附于血管内皮,抗氧化,抗炎作用,抗血栓和促纤溶等多方面作用。本文主要阐述高密度脂蛋白及其亚型抗血栓形成机制。其主要机制是通过上调内皮一氧化氮合酶表达和促进一氧化氮合酶生成来促进血管保护因子一氧化氮的合成,同时还通过激活前列环素合成,减少组织因子表达,经蛋白C途径下调凝血酶生成,直接或间接地减少血小板聚集,减少凝血和促进纤溶来对抗血栓形成。     

高密度脂蛋白与动脉粥样硬化关系的研究进展

临床流行病学已经证实高密度脂蛋白胆固醇水平与心血管意外的风险呈负相关。高密度脂蛋白通过促进胆固醇酯的逆向转运,减少胆固醇在外周组织和血管的沉积;抑制低密度脂蛋白的物理和化学修饰从而减少泡沫细胞的形成;降低黏附分子和巨噬细胞趋化蛋白的活性从而抑制慢性炎症;减轻内皮功能的紊乱而发挥心血管的保护作用已经成为共识。然而,随着多项以升高高密度脂蛋白水平,逆转动脉硬化进程为目的的研究结果的公布,对高密度脂蛋白有了新的评价,认为高密度脂蛋白的功能比水平更为重要,高密度脂蛋白胆固醇与心血管疾病的关系还有待探索。     

抗动脉粥样硬化药现状与进展

动脉粥样硬化 (ＡＳ)是缺血性心脑血管疾病的病理病生基础 ,与许多疾病的发生都有关系 ,也是中老年人最常见的疾病之一。由于ＡＳ的发病机理复杂 ,与许多因素有关 ,所以 ,抗动脉粥样硬化药的研究、应用发展很快 ,种类很多。药物的作用主要包括两个方面 :一是消除、控制诱发ＡＳ的各种因素 ,如血脂代谢紊乱、高血压等 ;二是防治ＡＳ的并发症和血栓形成。以下简要加以简介。1　调血脂药 :ＡＳ发生的原因尚未完全明确。ＡＳ早期的病理表现 ,是动脉以内膜下层平滑肌细胞与泡沫细胞的出现和胆固醇 (Ｃｈ)脂类物质的沉积为主要特点[1,2 ] 。动物实…     

高密度脂蛋白亚型分布同冠心病关系的研究进展

高密度脂蛋白是一类功能、组成、密度、颗粒大小极不均一的脂蛋白,其各亚型的分布同冠心病密切相关。通过研究高密度脂蛋白亚型代谢同冠心病的关系将会对更加深入的了解冠心病的发病机制及开发新一代的降脂药具有重要的指导意义。     

高密度脂蛋白功能与动脉粥样硬化

冠心病是东西方各国发病和死亡的第一位原因。冠状动脉粥样硬化是多因素疾病,从危险因素的作用,内皮功能的失调,致动脉粥样硬化脂蛋白滞留于动脉壁,炎症反应,到泡沫细胞和纤维斑块的形成,斑块破裂和血栓形成,构成了冠心病发生、发展和转归的序列过程。在众多的危险因素中,胆固醇升高是具有因果性致病性因子,     

人血浆高密度脂蛋白亚类分布与动脉粥样硬化

高密度脂蛋白(HDL)是一类不均一的脂蛋白,各种HDL亚类具有不同而又相关的代谢功能.血浆脂质和载脂蛋白含量变化会影响HDL亚类分布.高甘油三酯血症、高胆固醇血症、特别是混合型高脂血症患者血浆HDL颗粒变小,而且随着血浆甘油三酯、总胆固醇含量的升高,上述变化会更加明显.提示HDL成熟代谢受阻,胆固醇逆向转运减弱.不同的载脂蛋白在HDL合成及代谢中起着各不相同的作用.当血浆apoAⅠ含量增加时,所有的HDL亚类均增加,且大颗粒的HDL2b增加最为明显.ApoAⅡ具有双重功能,有使小颗粒HDL3b、HDL3a以及大颗粒的HDL2b同时增加的作用.血浆apoB100、CⅡ以及CⅢ在HDL组装中具有协同作用,apoAⅠ对抗上述载脂蛋白引起HDL颗粒变小的作用.此外,糖尿病和冠心病患者血浆HDL颗粒呈变小趋势.使用他汀治疗的冠心病患者血浆HDL亚类分布的改善滞后于血浆脂质水平的正常化,表明HDL亚类图谱分析有助于冠心病患者的风险分层.     

高密度脂蛋白抗动脉粥样硬化作用

高密度脂蛋白抗动脉粥样硬化作用刘秉文，曾成林（华西医科大学生物化学与分子生物学研究所成都６１００４１）血浆高密度脂蛋白（ＨＤＬ）的密度为１．０６３～１．２１０，其电泳迁移率处于α－带，又称为α—脂蛋白，主要由肝脏和肠道合成。ＨＤＬ含蛋白质５０％～５５...     

高密度脂蛋白抗动脉粥样硬化的研究进展

低水平的血浆高密度脂蛋白胆固酵(HDL-C)是冠心病的独立危险因子，HDL—C与冠心病的发病呈负相关。高密度脂蛋白(HDL)通过多种机制发挥其抗动脉粥样硬化的作用：它具有抗低密度脂蛋白氧化修饰的作用，减少脂质的摄取沉积；参与胆固醇的逆向转运，促进胆固醇从血管壁排出，将其运送至肝脏清除，并增加粥样硬化斑块的稳定性，减少斑块破裂。此外，它还能保护内皮屏障功能，介导内皮依赖性舒张，并降低粘附分子的表达，具有冠脉保护作用。本文主要阐述HDL抗动脉粥样硬化机制研究的新进展。     

氧化修饰高密度脂蛋白与动脉粥样硬化

血浆高密度脂蛋白 (HDL)与低密度脂蛋白(1DL)一样 ,可以被氧化修饰 ,体内多种因素均具有氧化修饰HDL ,形成氧化修饰的高密度脂蛋白 (ox -HDL)的作用 ,HDL被氧化后化学组成与理化性质发生改变 ,不但失去抗动脉粥样硬化 (AS)的作用 ,反而具有致AS作用。维生素C和维生素E的摄入有可能有助于防止HDL的氧化。     

氧化型高密度脂蛋白与动脉粥样硬化

高密度脂蛋白(HDL)在体内经过髓过氧化物酶氧化形成不同位点修饰的HDL(ox-HDL),ox-HDL通过损伤内皮细胞、影响胆固醇逆转运过程、促进平滑肌增生等方式降低抗动脉粥样硬化的作用。因此HDL不同位点的氧化修饰及相关功能改变或将为治疗动脉粥样硬化提供新的思路。     

冠脉狭窄度与高密度脂蛋白亚类关系分析

目的探讨冠脉造影患者冠状动脉狭窄程度和高密度脂蛋白(High-density lipoprotein,HDL)亚类的关系。方法 1抽取2013年至2015年因疑诊冠心病(Coronary Heart Disease,CHD)入住我院老年医学科、心内科行冠状动脉造影(Coronary arteriography,CAG)的患者361例,通过CAG确诊为CHD患者(至少有一支冠状动脉或分支狭窄50%)237例,其中男138例,女99例,平均年龄(60.31±8.59),未诊断CHD患者124例,男50例,女74例,平均年龄(59.22±13.23);2抽取患者空腹12 h静脉血,选择双向电泳加免疫印迹检测法24h内测定HDL亚类,对患者冠脉造影结果(采用Gensini评分)评价冠状动脉狭窄程度;3计量资料用χ軘±s表示,定性资料用χ2检验,两组比较采用独立样本的t检验,logisitic回归分析与冠心病相关因素,有序Ordinal回归分析与冠状动脉狭窄程度的关系。结果 1 CHD组中中、重度患者组Preβ1-HDL、HDL3b较非CHD组明显增高(p0.05),CHD组中轻、中、重度患者组HDL3c较非CHD组明显增高(p0.05),而HDL2b较非CHD组显著减少(p0.05),随着冠状动脉狭窄程度的增加,Preβ1-HDL、HDL3b、HDL3c出现增高趋势,而HDL2b则降低;2二元Logistic回归分析,HDL亚类中Preβ1-HDL,HDL3b,HDL3c与CHD呈正相关(p0.05),HDL2b与CHD呈负相关;有序Ordinal回归,Preβ1-HDL与冠状动脉狭窄程度呈正相关,HDL2b与冠状动脉狭窄程度呈负相关。结论 Preβ1-HDL、HDL3b高对冠心病有风险,HDL2b是冠心病保护因素,在临床诊断治疗中,HDL2b值有可能做为冠心病预测因素,Preβ1-HDL、HDL2b可为预测和诊断CHD提供重要参考依据,冠心病的防治不仅要改善和促进胆固醇逆转运还要调节血脂及调整HDL亚类的构成比。     

高密度脂蛋白亚类与心血管疾病的现状分析

高密度脂蛋白是一类异质性脂蛋白,其亚类表现出在抗动脉粥样硬化功能和心血管保护作用方面的差异性,并随年龄、性别等的差异也发生动态变化。影响高密度脂蛋白功能和亚类分布的药物或许是改善心血管风险更有效的方法。文章就高密度脂蛋白亚类的检测、抗动脉粥样硬化功能以及与心血管疾病的相关性等进行综述,为人类心血管疾病的防治提供新视角。     

多廿烷醇联合阿托伐他汀治疗对高脂血症患者高密度脂蛋白颗粒的影响

目的 探讨多廿烷醇联合阿托伐他汀和单用阿托伐他汀治疗对高脂血症患者血脂水平及高密度脂蛋白(HDL)颗粒的影响。方法 选择高脂血症患者49例,随机分为3组,分别为安慰剂对照组(n=17)、阿托伐他汀20 mg治疗组(n=16)和多廿烷醇20 mg联合阿托伐他汀20 mg治疗组(n=16,联合治疗组)。Lipoprint脂蛋白分类检测仪对HDL颗粒进行分类。治疗8周后比较3组治疗前后血脂指标及HDL颗粒的变化,分析多廿烷醇联合阿托伐他汀和单用阿托伐他汀治疗对HDL颗粒的影响。结果 与治疗前比较,治疗后阿托伐他汀组和联合治疗组的甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)浓度均降低(P0.05,P0.001),而高密度脂蛋白胆固醇(HDLC)浓度的差异均无统计学意义(P0.05)。经阿托伐他汀治疗后,大颗粒HDLC浓度及百分比均显著升高(P0.05),而小颗粒HDLC浓度及百分比均显著降低(P0.05)。在联合治疗组,大颗粒HDLC浓度及百分比明显增加(P0.05),小颗粒HDLC浓度及百分比均明显降低(P0.001)。联合治疗组小颗粒HDL浓度和百分比的降低值显著大于阿托伐他汀组。结论 阿托伐他汀组和联合治疗组均显著改善高脂血症患者的HDL颗粒分布,增加大颗粒HDLC浓度及百分比,同时降低小颗粒HDLC的浓度及百分比;多廿烷醇联合阿托伐他汀降低小颗粒HDLC浓度与百分比的效果明显优于阿托伐他汀单独治疗组。     

High-density lipoprotein and atherosclerosis: Roles of lipid transporters

Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.     

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.     

高密度脂蛋白对3T3-L1脂肪细胞分泌白细胞介素8的影响

分别用不同浓度高密度脂蛋白(HDL,0、10、50和100μg/ml)孵育3T3-L1脂肪细胞16 h,再加入100 ng/ml脂多糖共同孵育6 h.用酶联免疫吸附法(ELISA)检测各组脂肪细胞培养液中的白细胞介素8水平,半定量逆转录多聚酶链式反应(RT-PCR)测定脂肪细胞PPARγmRNA的表达.结果 显示,脂多糖刺激使脂肪细胞分泌白细胞介素8增加(P＜0.05).不同浓度HDL干预的脂肪细胞分泌的白细胞介素8水平均低于脂多糖刺激组,并且呈剂量依赖性.不同浓度HDL干预的脂肪细胞PPARγmRNA表达较单用脂多糖刺激组显著升高.这些结果提示HDL可能通过上调PPARγ的表达、抑制脂肪细胞分泌白细胞介素8分泌.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia

Aim: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. Methods: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent‐to‐treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low‐density lipoprotein cholesterol (LDL‐C) subclasses LDL₁‐C, LDL₂‐C and LDL₃‐C; real LDL‐C (LDL‐C^r); intermediate‐density lipoprotein cholesterol (IDL‐C), IDL₁‐C, IDL₂‐C; very low‐density lipoprotein cholesterol (VLDL‐C), VLDL₃‐C; and remnant‐like lipoprotein cholesterol (RLP‐C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high‐density lipoprotein cholesterol (HDL‐C) subclass HDL₃‐C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL_{1 + 2}‐C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL₄‐C and LDL‐C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL₂‐C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL‐C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. Conclusions: Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.     

Glycation of high-density lipoprotein triggers oxidative stress and promotes the proliferation and migration of vascular smooth muscle cells

Background In type 2 diabetes mellitus (T2DM), high-density lipoprotein (HDL) impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compositions and modifications. In this study, we examined the effects and the related mechanisms of glycation of HDL on the proliferation and migration of vascular smooth muscle cells (VSMCs). Methods & Results Glycated HDL (G-HDL) was modified with D-glucose (25 mmol/L) in vitro. Diabetic HDL (D-HDL) was isolated from T2DM patients. Rat VSMCs were isolated from the thoracic aortas. Human VSMCs were obtained from ScienCell Research Laboratories. Alpha-actin was detected through immunofluorescence. VSMC proliferation was assayed by Cell Count. VSMC migration was determined by transwell chamber and scratch-wound assay. Intracellular reactive oxygen species (ROS) was detected based on ROS-mediated 2'',7''-dichlorofluorescein (DCFH-DA) fluorescence. Compared to native HDL (N-HDL), G-HDL remarkably promoted VSMC proliferation and migration in the dose and time-dependent manners. In addition, G-HDL enhanced ROS generation in VSMCs. However, the ROS scavenger, N-acetylcysteine, efficiently decreased ROS production and subsequently inhibited the proliferation of VSMCs induced by G-HDL. Similarly, D-HDL from T2DM patients also promoted ROS release and VSMC proliferation and migration. Conclusions HDL either glycated in vitro or isolated from T2DM patients triggered VSMC proliferation, migration, and oxidative stress. These results might partly interpret the higher morbidity of cardiovascular disease in T2DM patients.