低密度脂蛋白胆固醇升高在家兔动脉粥样硬化发生发展中的意义

目的观察低密度脂蛋白胆固醇(LDL-c)对家兔动脉粥样硬化(AS)形成的影响,探讨AS的发生机制。方法以高脂饲料复制家兔实验性AS模型,分阶段检测家兔血清胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-c)和低密度脂蛋白胆固醇(LDL-c)含量;观察主动脉内膜病理学变化;分析主动脉内膜增生程度及AS斑块面积与血浆脂蛋白水平的相关性。结果高脂组家兔主动脉粥样硬化面积和内膜增生程度明显较对照组增加(P<0.01),血浆LDL-c水平明显较对照组升高(P<0.01);动脉内膜增生程度及AS斑块面积均与血浆LDL-c水平呈非常显著正相关(r=0.837,P<0.001)。结论提示血浆LDL-c水平升高,是致AS发生发展的重要原因。     

ABCA1在动脉粥样硬化发生与发展中的作用

腺苷三磷酸结合盒转运体A1(ATP binding cassette transporter A1 ,ABCA1)是一种整合膜蛋白,它以ATP为能源,促进细胞内游离胆固醇和磷脂的流出,在胆固醇逆转运(RCT)和HDL生成的起始步骤中起重要作用,被称作RCT守门人。核受体PPARs、LXRs和FXR对ABCA1蛋白的表达具有调控作用。人体50种组织中存在有ABCA1 mRNA,在胰、肝、肺、肾上腺和胎儿组织中ABCAl表达水平最高,ABCAl功能障碍将导致巨噬细胞内大量的胆固醇沉积而成为泡沫细胞,继而漫润血管壁,促进As的发生发展。     

炎症小体在动脉粥样硬化发生发展中的研究进展

炎症小体(inflammasome)是免疫细胞内由多种蛋白质所组成的复合体,属于胞浆型模式识别受体(pattern recognition receptor,PRR)。它作为固有免疫系统的重要组分在机体免疫反应和疾病发生过程中具有重要作用。近年来的研究表明炎症小体是炎症免疫反应的核心。由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD样受体蛋白-3)炎症小体在多种疾病过程中,包括动脉粥样硬化症、家族性周期性自身炎症反应、阿尔海默茨病和2型糖尿病等都发挥了关键作用。因此,NLRP3(NOD样受体蛋白-3)炎症小体可能为各种炎症性疾病,包括动脉粥样硬化的治疗提供新的靶点。本文将对炎症小体在动脉粥样硬化发生发展中发挥的作用进行综述。     

直接法测定低密度脂蛋白胆固醇

为了提高血脂检验技术,探讨直接法测定低密度脂蛋白胆固醇(LDL-C),选用市售的两种直接测定LDL-C的试剂盒进行方法学的实验评价,结果表明：直接法具有简便、快速、准确和适合自动分析等特点.两种试剂盒的测定结果都能满足建立分析方法要求的目标,不精密度＜４％,两法显著相关r=0.994, y=1.0572x－0.1052, S_y/x=0.1913,且各种方法学检验结果相近,使用者可结合实际选作常规测定之用.     

LOX-1与动脉粥样硬化

氧化低密度脂蛋白(oxidizedlow-densitylipoprotein,Ox-LDL)是修饰脂蛋白中的一种,其与动脉粥样硬化的发生发展密切相关。1997年,Sawamura等在牛主动脉内皮细胞上发现了Ox-LDL的一种新型受体,即植物凝集素样氧化型低密度脂蛋白受体-1(lectin-likeoxidizedlowdensitylipoproteinreceptor-1,LOX-1),其在结构和功能上不同于其他类型的巨噬细胞清道夫受体。该文介绍LOX-1在近几年来的一些研究新进展,及其与动脉粥样硬化发病机制间的相互关系。     

冠心病患者低密度脂蛋白与血小板GMP-140水平相关性研究

目的：探讨冠心病患者低密度脂蛋白与血小板功能活化产物GMP-140的关系。方法：应用酶联免疫分析法对120例研究对象进行了血浆LDL、GMP-140水平的测定,其中包括急性冠脉综合征组40例,稳定性心绞痛组40例,并与40例正常健康人作比较。结果：ACS患者血浆LDL和GMP-140水平均非常显著的高于正常人组（P〈0.01）,ACS组又高于SAP组（P〈0.05）,且血浆LDL与GMP-140水平呈正相关。结论：检测CHD患者血浆LDL和GMP-140水平的变化对CHD的发生和发展以及疗效和预后观察均具有重要的临床意义。     

冠心病患者低密度脂蛋白与血小板GMP-140水平相关性研究

目的:探讨冠心病患者低密度脂蛋白与血小板功能活化产物GMP-140的关系。方法:应用酶联免疫分析法对120例研究对象进行了血浆LDL、GMP-140水平的测定,其中包括急性冠脉综合征组40例,稳定性心绞痛组40例,并与40例正常健康人作比较。结果:ACS患者血浆LDL和GMP-140水平均非常显著的高于正常人组(P<0.01),ACS组又高于SAP组(P<0.05),且血浆LDL与GMP-140水平呈正相关。结论:检测CHD患者血浆LDL和GMP-140水平的变化对CHD的发生和发展以及疗效和预后观察均具有重要的临床意义。     

极低密度脂蛋白受体研究进展

极低密度脂蛋白受体 (VLDL R)属于低密度脂蛋白受体 (LDL R)超家族 ,结构上与LDL R极为相似 ,而在结合特性、组织分布及生理功能上存在较大的差异 .近年来的研究表明 ,VLDL R配体结合域中的重复序列参与配体的结合 ,并已初步确定受体N端的 4个重复序列中含有与配体结合的重要位点 ;在哺乳动物体内 ,VLDL R主要分布于脂代谢活跃的组织细胞 ,如 :心肌、骨骼肌和脂肪组织等 ,表明其与脂质尤其是甘油三酯的代谢密切相关 ;动脉粥样硬化 (AS)的病变斑块组织中该受体的表达量很高 ,推测VLDL R参与了AS的病变过程 ;在不同的细胞内 ,VLDL R及其亚型的表达并不一致 ,并发现与各种生理、病理变化相关 ,已经发现多种转录因子参与VLDL R表达的调控 ;基因敲除研究也不断揭示VLDL R新的功能意义 ,特别是发现了VLDL R在脑的发育过程中的重要信号作用 ,这些研究已使人们对VLDL R有了新的更全面的认识     

Low Serum High Density Lipoprotein Cholesterol Concentration is an Independent Predictor for Enhanced Inflammation and Endothelial Activation

Background

Inflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established.

Objectives

(1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.

Methods

422 subjects (mean age±SD = 43.2±11.9years) of whom 207 had low HDL-c concentrations (HDL-c <1.0mmol/L and <1.3mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].

Results

Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F₂-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.

Conclusion

Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.     

Effect of Circulating Forms of Soy Isoflavones on the Oxidation of Low Density Lipoprotein

Soy isoflavones are thought to have a cardioprotective effect that is partly mediated by an inhibitory influence on the oxidation of low density lipoprotein (LDL). However, the aglycone forms investigated in many previous studies do not circulate in appreciable quantities because they are metabolised in the gut and liver. We investigated effects of various isoflavone metabolites, including for the first time the sulphated conjugates formed in the liver and the mucosa of the small intestine, on copper-induced LDL oxidation. The parent aglycones inhibited oxidation, although only 5% as well as quercetin. Metabolism increased or decreased their effectiveness. Equol inhibited 2.65-fold better than its parent compound daidzein and 8-hydroxydaidzein, not previously assessed, was 12.5-fold better than daidzein. However, monosulphated conjugates of genistein, daidzein and equol were much less effective and disulphates completely ineffective. Since almost all isoflavones circulate as conjugates, these data suggest that despite the increased potency produced by some metabolic changes, isoflavones may not be effective antioxidants in vivo unless they are deconjugated again.