脑梗死患者血浆HDL亚类组成及含量研究

目的:分析脑梗死患者血浆高密度脂蛋白(HDL)亚类组成及含量。方法:采用双向电泳-免疫印迹检测法分析50例脑梗死患者和50例正常者HDL亚类的组成及含量。结果:与对照组比较,脑梗死患者血浆中preβ2-HDL和HDL2b含量显著降低(均P<0.01),小颗粒preβ1-HDL含量显著增加(P<0.01);患者血浆三酰甘油(TG)水平与preβ1-HDL、HDL3b、HDL2a和HDL2b含量呈显著负相关(均P<0.05),HDL-C、载脂蛋白AⅠ含量与preβ1-HDL、preβ2-HDL、HDL3c、HDL3b、HDL3a、HDL2a和HDL2b含量呈显著正相关(均P<0.05)。结论:脑梗死患者血浆大颗粒HDL含量明显降低,小颗粒HDL含量明显增加,提示脑梗死患者HDL代谢过程异常。     

代谢综合征患者血浆甘油三酯水平对HDL亚类分布的影响

目的探讨代谢综合征(MS)患者血浆甘油三酯(TG)水平对高密度脂蛋白(HDL)亚类分布的影响。方法选取在南华大学附属第一医院就诊的MS患者血样,全自动生化分析仪测定血脂含量及载脂蛋白浓度,根据美国国家胆固醇教育计划NCEP ATP-Ⅲ文件,将MS患者按TG浓度分4组,即TG1.69 mmol/L、1.69mmol/L≤TG2.25 mmol/L、2.25 mmol/L≤TG5.64 mmol/L、TG≥5.64 mmol/L,采用双向电泳-免疫印迹检测法测定MS患者和99例正常人血浆HDL亚类的相对含量。结果与对照组相比,MS患者血浆总胆固醇(TC)、TG、低密度脂蛋白胆固醇(LDLC)、载脂蛋白B100(Apo B100)、preβ1-HDL、HDL3b含量及Apo B100/AⅠ和LDLC/HDLC比值均显著性增高(P0.05或P0.001),HDLC、Apo AⅠ、HDL2b、HDL2a显著降低(P0.05或P0.001)。并且随着血浆TG水平的升高,小颗粒的preβ1-HDL、HDL3a和HDL3b含量升高,而大颗粒的HDL2b和HDL2a含量降低。结论MS患者HDL亚类分布异常,小颗粒的preβ1-HDL和HDL3b含量升高,而大颗粒的HDL2b和HDL2a含量降低,血浆TG含量变化可能是影响MS患者HDL亚类异常的因素之一。     

血浆胆固醇含量对代谢综合征患者HDL亚类分布的影响

目的探讨代谢综合征(MS)患者血浆胆固醇水平对高密度脂蛋白(HDL)亚类分布的影响。方法采用全自动生化分析仪测定MS患者血浆血脂含量及载脂蛋白浓度,用双向电泳-免疫印记法测定血浆HDL亚类的含量。并根据中国成人血脂异常防治指南,将MS患者按血浆总胆固醇(TC)浓度分为3组,即TC正常范围组:TC5.17 mmol/L、TC临界升高组:5.17 mmol/L≤TC6.21 mmol/L、TC升高组:TC≥6.21 mmol/L。结果与对照组相比,MS患者血浆空腹血糖(FPG)、TC、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、载脂蛋白B100(apo B100)、preβ1-HDL、HDL3b含量及apo B100/AI和LDLC/HDLC比值均显著性增高(P0.05或P0.001),HDLC、apo AI、HDL2a、HDL2b显著降低(P0.05或P0.001);并且随着血浆TC水平的升高,小颗粒的preβ1-HDL和HDL3b含量升高,而大颗粒的HDL2a和HDL2b含量降低。MS患者HDLC的含量降低和(或)LDLC含量升高都存在不同程度的血浆HDL亚类分布异常,而且HDLC含量异常时存在HDL各亚类分布异常的程度较LDLC含量异常时更显著;当二者同时异常时,小颗粒的preβ1-HDL增加,大颗粒的HDL2b减少更加明显。直线相关和多元回归分析中发现,血浆TC、HDLC和LDLC含量紊乱与HDL亚类异常分布存在关联。结论 MS患者胆固醇含量与HDL亚类分布异常有关。     

代谢综合征患者白细胞介素6水平与HDL亚类分布的相关性分析

目的探究代谢综合征(MS)患者血浆白细胞介素6(IL-6)水平与高密度脂蛋白(HDL)亚类分布及其相关性。方法收集MS组患者135例和对照组健康体检人群77例的血样,酶联免疫吸附法(ELISA)测定IL-6含量,按IL-6浓度将MS患者分为低IL-6组(IL-6≤66.76 ng/L)、中IL-6组(66.76 ng/LIL-6113.84 ng/L)、高IL-6组(IL-6≥113.84 ng/L)。双向电泳-免疫印迹法测定血浆HDL亚类的相对含量,全自动生化分析仪测定血脂浓度及载脂蛋白含量。分析不同性别对IL-6、血脂、载脂蛋白及HDL亚类分布的影响,及IL-6水平与HDL亚类分布的相关性。结果与对照组比较,MS组IL-6、preβ1-HDL、HDL3b、HDL3c、TC、TG、LDLC含量以及LDLC/HDLC和Apo B100/Apo AI均显著增高(P0.05或P0.01),而HDL2a、HDL2b、preβ2-HDL、Apo AI和HDLC含量显著降低(P0.05或P0.01)。与对照组同性别比较,MS组男性或女性HDL亚类的相对含量有差异(P0.05或P0.01);与同组男性比较,对照组和MS组女性血脂、血浆载脂蛋白水平差异均无统计学意义(P0.05)。MS患者血浆IL-6含量的升高与HDL亚类分布异常存在相关性,即IL-6的含量与小颗粒的preβ1-HDL、HDL3b水平呈正相关,与大颗粒HDL2b水平呈负相关。结论 MS患者血浆IL-6水平升高,且HDL颗粒呈变小趋势,高水平的IL-6可能与HDL亚类分布异常和血脂紊乱有关。     

2型糖尿病患者血清HDL亚类组成的研究

目的研究2型糖尿病患者血清HDL亚类组成及相对百分含量的变化.方法采用双向电泳-免疫印迹检测法分析了38例正常对照及38例患者血清HDL亚类组成及相对百分含量.结果患者血清中前β1-HDL(P＜0.001)、前β2-HDL及HDL3a(P＜0.05)含量显著增加,而HDL2a(P＜0.05)及HDL2b(P＜0.001)含量显著减少.患者空腹血糖及血清TG浓度与前β1-HDL、HDL3c及HDL3a水平呈显著正相关,而与HDL2b水平呈显著负相关.结论2型糖尿病患者血清HDL颗粒直径呈变小趋势,提示患者HDL成熟代谢过程受阻.     

肥胖伴糖耐量异常者经吡格列酮治疗后血清脂蛋白亚类的变化

目的　研究肥胖伴糖耐量异常者血高密度脂蛋白（HDL）亚类分布情况以及吡格列酮干预后对血浆HDL亚类分布的影响。方法　比较40例健康人与40例肥胖伴糖耐量异常者血浆高密度脂蛋白（HDL）亚类分布,了解肥胖伴糖耐量异常者血浆HDL亚类分布特点。采用配对设计的随机分组方法,以性别作为随机配对的条件,将40例肥胖伴糖耐量异常者作为研究对象分为安慰剂组和吡格列酮组,药物干预12周后,抽取受试者空腹12　h静脉血,24　h内进行HDL各亚组分含量的测定以及对氧磷酶1（PON-1）活性的测定。分析血浆HDL亚类分布与PON-1活性的相关性。结果　肥胖伴糖耐量异常者血清HDL分布异常,HDL2a和HDL2b减低,而小颗粒的preβ1-HDL、preβ2-HDL、HDL3a升高,差异具有统计学意义（P<0.05）。与安慰剂组比较,吡格列酮组用药后12周,受试者血清HDL中HDL2a、HDL2b、PON-1显著升高,preβ1-HDL显著降低,差异具有统计学意义（P<0.05）。相关性分析显示,preβ1-HDL与PON-1呈负相关,　HDL2b与PON-1呈正相关,相关性有显著性。结论　肥胖伴糖耐量异常患者血清中HDL亚类分布异常,成熟代谢过程受阻,趋向于较弱的抗动脉粥样硬化的分布趋势。吡格列酮通过改善HDL亚类的分布以及提高PON-1活性,增强了HDL抗动脉粥样硬化的作用。HDL亚类分布中成熟的大颗粒含量越高,PON-1的活性越强,抗动脉粥样硬化能力越强。     

血浆晚期氧化蛋白产物与HDL亚类组成的关系

目的 探讨血浆晚期氧化蛋白产物(AOPPs)对血浆高密度脂蛋白(HDL)亚类组成及含量的影响.方法 采用氯胺-T法和双向电泳免疫印迹检测法对346例受试者分别测定血浆AOPPs的相对含量和血浆HDL亚类的组成及含量.按AOPPs浓度均值加或减去一个标准差作为分割点,将受试者分为3组,即低AOPPs(AOPPs≤60μmol/L)组、中AOPPs(60 μmol/L＜ AOPPs ＜90 μmol/L)组、高AOPPs(AOPPs ≥90μmol/L)组.结果 与低AOPPs组相比,高AOPPs组中preβ1-HDL及HDL3a显著增多(P＜0.001),而HDL2a、卵磷脂胆固醇酰基转移酶及HDL2b显著降低(P＜0.001),各组胆固醇酯转运蛋白无变化.相关性分析表明AOPPs与血浆HDL亚类分布存在显著相关.结论 随着血浆AOPPs水平的升高HDL颗粒有变小的趋势,AOPPs可能阻碍了HDL的成熟代谢.     

冠心病患者血脂水平与血清高密度脂蛋白亚类组成关系的研究

目的 :探讨冠心病 (CHD)患者血脂水平与血清高密度脂蛋白 (HDL)亚类组成的关系。方法 :采用双向电泳 免疫印迹检测法分析了 83例CHD患者血清HDL亚类组成及相对百分含量。结果 :按血清三酰甘油 (TG)浓度将CHD患者分为 4组 ,各组患者血清中前β1 HDL、HDL3c(除TG <1.35mmol L组外 )、HDL3b水平显著高于对照组 (P <0 .0 0 1) ,HDL2b水平显著低于对照组 (P <0 .0 1)。随着血清TG浓度的升高 ,前 β1 HDL、HDL3c及HDL3b颗粒逐渐增加 ,而HDL2a及HDL2b颗粒逐渐减少。按血清HDL胆固醇 (HDL C)浓度将CHD患者分为 3组 ,各组患者中 ,前 β1 HDL(除HDL C≥ 1.30mmol L组外 )、HDL3c及HDL3b水平显著高于对照组 (P <0 .0 5～ <0 .0 1) ,HDL2b水平显著低于对照组 (P <0 .0 1)。随着血清HDL C浓度的升高 ,前 β1 HDL、HDL3c、HDL3b及HDL3a颗粒逐渐减少 ,而HDL2b颗粒逐渐增加。结论 :CHD患者血清HDL颗粒直径呈变小趋势 ,并且随着TG水平的升高和HDL C水平的降低 ,其HDL颗粒的变小程度更加明显。     

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。     

代谢综合征患者血浆网膜素1水平与HDL亚类分布的相关性分析

目的探讨代谢综合征(MS)患者血浆网膜素1(Omentin-1)水平对高密度脂蛋白(HDL)亚类分布的影响。方法收集在南华大学附属医院就诊的MS患者102例和对照组81例的血样,采用全自动生化分析仪测定血脂浓度及载脂蛋白含量,酶联免疫吸附法测定Omentin-1的含量,双向电泳-免疫印迹法测定人血浆HDL亚类的相对含量。按Omentin-1浓度均值加减去一个标准差作为分割点,将MS患者分为3组:低Omentin-1组(Omentin-1≤9.10μg/L)、中Omentin-1组(9.10μg/LOmentin-126.68μg/L)、高Omentin-1组(Omentin-1≥26.68μg/L)。结果随着Omentin-1浓度的降低,MS患者血浆甘油三酯(TG)、总胆固醇(TC)及ApoB100/AⅠ和LDLC/HDLC比值均显著性增高(P0.05或P0.01),高密度脂蛋白胆固醇(HDLC)、ApoAⅠ含量显著降低(P0.05或P0.01)。与低Omentin-1组相比,高Omentin-1组中小颗粒的preβ1-HDL和HDL3b含量显著下降(P0.05或P0.01),而大颗粒的HDL2a含量显著上升(P0.05)。结论 MS患者血浆Omentin-1水平降低,且HDL颗粒呈变小趋势,低水平的Omentin-1可能与HDL亚类分布异常和血脂紊乱有关。     

The relationship between high density lipoprotein subclass profile and apolipoprotein concentrations

The HDL fraction in human plasma is heterogeneous in terms of size, shape, composition, and surface charge. The HDL subclasses contents were quantified by 2-dimensional non-denaturing gel electrophoresis, immunoblotting, and image analysis. This research review systematically analyzed the relationship between the contents of HDL subclasses and the concentrations and ratios of the 5 major plasma apolipoproteins (apo). As the concentration of apoA-I increases, the contents of all HDL subclasses increase significantly. The most significant association was observed between large-sized HDL2b contents and apoA-I. ApoA-II played a dual function in the contents of HDL subclasses, and both small-sized HDL3b and HDL3a and large-sized HDL2b tended to increase with apoA-II concentration. An increase in the concentrations of apoC-II, C-III, and B-100 resulted in higher levels of small-sized HDL particles and lower levels of large-sized HDL particles. Plasma apoB- 100, apoC-II, and apoC-III appear to play a coordinated role in assembly of HDL particles and the determination of their contents. Higher concentrations of apoA-I could inhibit the reduction in content of large-sized HDL2b effected by apoB-100, C-II, and C-III. The preβ1-HDL contents increased significantly and those of HDL2b declined progressively with an increased apoB-100/apoA-I or a decreased apoC-III/apoC-II ratio. In summary, each apo has distinct but interrelated roles in HDL particle generation and metabolism. ApoA-I and apoC-II concentrations are independent determinants of HDL subtypes in circulation and apoA-I levels might be a more powerful factor to influence HDL subclasses distribution. Moreover, apoB- 100/apoA-I ratio could reliably and sensitively reflect the HDL subclass profile.     

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased preβ₁-HDL, HDL_3c, HDL_3b (only in the highest tertile of apo C-III group), and HDL_3a, but decreased HDL_2a and HDL_2b contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized preβ₁-HDL increased successively and significantly; but those of large-sized HDL_2b reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of preβ₁-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL_2b; on the contrary, HDL_2b declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with preβ₁-HDL, preβ₂-HDL, and HDL_3a. The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL_2b particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.     

Relationship between total cholesterol/high-density lipoprotein cholesterol ratio, triglyceride/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442 Chinese subjects. The particle size of HDL shifted toward smaller size with the elevation of TC/HDL-C and TG/HDL-C ratios. The ratio of large-sized HDL(2b) to small-sized prebeta(1)-HDL (HDL(2b)/prebeta(1)-HDL) was about 4.7 in the subjects with TC/HDL-C of 3.3 or lower and TG/HDL-C of 2.5 or lower, whereas it was only approximately 1.1 in subjects with TC/HDL-C greater than 6 and TG/HDL-C greater than 5. Pearson correlation analysis revealed that the TC/HDL-C ratio was positively correlated with prebeta(1)-HDL and HDL(3a) but negatively correlated with HDL(2a) and HDL(2b), whereas the TC/HDL-C ratio was only inversely correlated with HDL(2b). The TC/HDL-C and TG/HDL-C ratios together may be a good indicator of HDL subclass distribution. When these 2 ratios increased simultaneously, the trend toward smaller HDL size was obvious, which, in turn, indicated that the maturation of HDL might be impeded and the reverse cholesterol transport might be weakened. In addition, the TG/HDL-C ratio might be a more powerful factor to influence the distribution of HDL subclasses.     

Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling

Probucol is a unique hypolipidemic agent that increases cholesteryl ester transfer protein (CETP) activity. Enhanced CETP-mediated conversion of high-density lipoprotein (HDL) partly explains the probucol-induced decrease in HDL cholesterol and increase in plasma preβ1-HDL (native lipid-poor HDL) concentrations. However, HDL cholesterol is reduced in patients that are completely deficient in CETP. Angiopoietin-like protein 3 (ANGPTL3) is an endogenous suppressor of endothelial lipase that promotes the hydrolysis of HDL phospholipids and may generate preβ1-HDL. To determine whether probucol decreases ANGPTL3 and HDL phospholipids while increasing preβ1-HDL, we measured these parameters before and after a 4-week probucol treatment in 39 hypercholesterolemic patients and age- and sex-matched controls. The median ANGPTL3 had decreased from 143 to 113 μg/L by week 4 (p < 0.05). High-performance liquid chromatography revealed that probucol decreased the phospholipid content of very large (13.5–15 nm) and large (12.1 nm) HDL particles predominantly by 65% (p < 0.01) and 53% (p < 0.001), respectively. The change in ANGPTL3, but not CETP mass, was positively correlated with that in large HDL phospholipids (r = 0.455, p < 0.05). The absolute and relative concentrations of preβ1-HDL increased by 14% (p < 0.01) and 60% (p < 0.001), respectively. The conversion rate of preβ1-HDL into α-migrating HDL by lecithin-cholesterol acyltransferase did not change significantly. In conclusion, probucol decreases plasma ANGPTL3 and HDL phospholipids while increasing preβ1-HDL. We speculate that probucol induces HDL remodeling via an endothelial lipase-mediated pathway.     

Lipoprotein distribution and composition in the human nephrotic syndrome

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.     

Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non-insulin-dependent diabetic subjects

High-density lipoprotein (HDL) plays an important role in the process of reverse cholesterol transport, which may become suboptimal with increasing body fatness. HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction. To determine how weight reduction affects HDL subclasses that are involved in reverse cholesterol transport, we studied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatty acids (MUFAs). Body weight, blood glucose, total cholesterol, and LDL cholesterol decreased after 8 and 12 weeks of weight reduction. With the very-low-fat diet, HDL cholesterol decreased significantly at 8 weeks, but recovered to initial levels after 12 weeks as body weight began to stabilize. Plasma apolipoprotein A-I (apo A-I) decreased substantially and significantly at 8 and 12 weeks with both diets, and was reflected in the reduction of apo A-I in HDL subclasses alpha1, alpha2, pre-beta1, and pre-beta2 + pre-beta3. The calculation of the percentage distribution of apo A-I among HDL species showed that only the proportion of pre-beta1-HDL decreased, whereas alpha2-HDL increased. This led to a significant increase in the alpha1 + alpha2/pre-beta ratio, ie, the ratio of the large cholesterol "storage" or "sink" HDL to the HDL "shuttle" fraction considered to be the initial acceptor of cell cholesterol. These data suggest that despite the reduction in HDL cholesterol and apo A-I, the redistribution of apo A-I in pre-beta1-HDL and alpha-HDL observed with weight reduction appears to revert to the pattern that we have previously reported in lean as opposed to overweight subjects.     

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.     

Bezafibrate increases prebeta 1-HDL at the expense of HDL2b in hypertriglyceridemia

Prebeta1-high density lipoprotein (prebeta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL(2) by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase prebeta1-HDL at the expense of HDL(2). To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, prebeta1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5+/-49.9 versus 72.5+/-34.1 mg/L apoA-I, P<0.01). Prebeta1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased prebeta1-HDL by 30% (160.2+/-64.5 mg/L apoA-I, P<0.05) but decreased HDL(2b) by 31% (from 188.8+/-94.9 to 129.3+/-78.7 mg/L apoA-I, P<0.05). Hepatic lipase activity increased by 24% (P<0.005). Prebeta1-HDL was generated either from ultracentrifugally isolated HDL(2) or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases prebeta1-HDL at the expense of HDL(2). We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.     

The association of lipoprotein and hepatic lipase activities with high density lipoprotein subclass levels in men with myocardial infarction at a young age

The relations between postheparin plasma lipase activities and concentrations of lipoproteins, in particular plasma high density lipoprotein (HDL) subclasses determined by gradient gel electrophoresis, were examined in 39 men who had survived a first myocardial infarction before the age of 45 years and in 20 age-matched control men. Reduced lipoprotein lipase (LPL) and hepatic lipase (HL) activities were found in the patients due to low LPL activity in patients with hypertriglyceridaemia, and low HL activity in those with a normal lipoprotein pattern or hypercholesterolaemia. Considerably lower plasma HDL2b and HDL2a protein concentrations and higher plasma HDL3b and HDL3c protein levels were found in the patients compared with the healthy control subjects. The subgroup of patients with hypertriglyceridaemia accounted for the major proportion of the case control differences for the HDL subspecies. However, significantly lower HDL2b and HDL2a concentrations were seen also among the normotriglyceridaemic patients. Analysis of the correlations between concentrations of HDL subclasses and lipase activities revealed positive associations between LPL and HDL2b and negative associations between HL and HDL2b. For LPL, this relationship was confined to hypertriglyceridaemic and for HL to normotriglyceridaemic subjects. HL was indicated to be positively connected with HDL3b levels, irrespective of lipoprotein pattern, whereas LPL seemed to be unassociated with HDL3b. It is concluded that low LPL and HL activities partly account for the change in HDL subclass distribution observed in patients with myocardial infarction at a young age.