血清甘油三酯含量与HDL亚类组成的关系

目的：探讨血TG含量对HDL亚类组成及含量的影响。 方法： 采用双向电泳－免疫印迹检测法按血清TG含量分层，分析了106例TC正常及147例高TC受试者血清HDL亚类组成及含量。 结果： 无论TC正常或高TC人群，血清小颗粒的per-β1-HDL含量在TG边缘性高（TC正常人群除外）、高TG以及TG极高亚组显著高于相应TG正常组 (P＜0.05及P＜0.01），而且颗粒较小的HDL3b及HDL3a含量也有相似的变化，其中高TG人群HDL3b在TG极高组，HDL3a在TG升高的各亚组均显著高于TG正常亚组(P＜0.05及P＜0.01）；与此相反，大颗粒的HDL2b在高TG组和TG极高组显著少于相应的TG正常亚组（p＜0.05），HDL2a也在高TC人群的TG极高组显著少于TG正常亚组（P＜0.05）。此外，与TC正常的相应亚组比较，高TC人群的per-β1-HDL（TG边缘性高亚组）及HDL3b（TG极高亚组）显著高于TC正常人群的相应亚组（P＜0.05及P＜0.01）。 结论： 随着TG、TC水平的升高，血清HDL颗粒呈变小趋势；TG、TC含量变化是影响HDL亚类组成的重要因素。     

血清总胆固醇、甘油三酯与高密度脂蛋白胆固醇比值同高密度脂蛋白亚类组成关系的研究

目的：探讨血清总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)、甘油三酯/高密度脂蛋白胆固醇（TG/HDL-C）比值与高密度脂蛋白（HDL）亚类组成及含量关系。 方法： 采用双向电泳-免疫印迹检测法分析了292例受试者血清HDL亚类的组成及含量。 结果： 随血清TC/HDL-C比值增大，preβ1-HDL、HDL3a含量升高，HDL2b、HDL2a含量降低。preβ1-HDL（P＜0.01，高比值组及中间组）、HDL3a（P＜0.05，高比值组）含量显著高于低比值组，而HDL2b（P＜0.01，高比值组及中间组）、HDL2a（P＜0.01，高比值组）含量显著低于低比值组；此外，高比值组preβ1-HDL、HDL3a含量显著高于中间组（P＜0.01，P＜0.05），而HDL2a、HDL2b含量显著低于中间组（P＜0.01，P＜0.01）。随血清TG/HDL-C比值增大，preβ1-HDL、HDL3a含量升高，HDL2b、HDL2a含量降低。preβ1-HDL、HDL3a（P＜0.01，P＜0.05，高比值组）含量显著高于低比值组，而HDL2b、HDL2a（P＜0.01，P＜0.01，高比值组及中间组）含量显著低于低比值组；此外，高比值组preβ1-HDL、HDL3a含量显著高于中间组（P＜0.01，P＜0.05），而HDL2a、HDL2b含量显著低于中间组（P＜0.01，P＜0.01）。相关分析发现，血清TC、TG、TC/HDL-C、TG/HDL-C与小颗粒preβ1-HDL含量呈显著正相关（P＜0.01，P＜0.01，P＜0.01，P＜0.01），与大颗粒HDL2b含量呈显著负相关（P＜0.05，P＜0.01，P＜0.01，P＜0.01）；HDL-C与小颗粒preβ1-HDL含量呈显著负相关（P＜0.05），与大颗粒HDL2b含量呈显著正相关（P＜0.01）。 结论： 血清TC/HDL-C＞5或TG/HDL-C＞2.2时，小颗粒HDL含量明显增加而大颗粒HDL含量明显减少，表明HDL成熟代谢过程受阻，胆固醇逆向转运作用减弱。     

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE:

Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids.

METHODS:

Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with ¹⁴C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions.

RESULTS:

The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The ¹⁴C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups.

CONCLUSION:

In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.     

Impairment of the ABCA1 and SR-BI-mediated cholesterol efflux pathways and HDL anti-inflammatory activity in Alzheimer's disease

The aim of our study was to investigate the effect of Alzheimer's disease (AD) on the cholesterol efflux capacity and anti-inflammatory activity of HDL. HDL and apoA-I were isolated from 20 healthy subjects and from 39 AD patients. Our results showed that serum- and HDL-mediated cholesterol efflux is significantly impaired in AD patients. This impairment of serum and HDL cholesterol efflux capacity was significantly inversely correlated to the AD severity as evaluated by MMSE scores. Results obtained from SR-BI-enriched Fu5AH and ABCA1-enriched J774 cells revealed that AD impaired the interaction of HDL and apoA-I with both the ABCA1 transporter and SR-BI receptor. Purified apoA-I from AD patients also failed to remove free excess cholesterol from ABCA1-enriched J774 macrophages. Interestingly, the decrease in plasma α-tocopherol content and the increase in MDA formation and HDL relative electrophoretic mobility indicated that AD patients had higher levels of oxidative stress. The anti-inflammatory activity of HDL was also significantly lower in AD patients as measured by the level of ICAM-1 expression. In conclusion, our study provides evidence for the first time that the functionality of HDL is impaired in AD and that this alteration might be caused by AD-associated oxidative stress and inflammation.     

The correlation between thyrotropin and dyslipidemia in a population-based study

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity.     

Effect of nicomol on high density lipoprotein (HDL) subfractions, HDL2e and HDL3e, separated by electrophoresis

High density lipoprotein (HDL) fractions were separated by dextran sulfate-Mg++ from sera of 5 healthy males before and after oral administration of a daily 1200 mg dose of Nicomol (2,2,6,6-tetrakis (nicotinoyloxymethyl) cyclohexanol; Cholexamin, Kyorin Pharmaceutical Co. Ltd.) for 2 weeks. The HDL fractions were further subdivided into HDL2e and HDL3e by Utermann's electrophoretic method on polyacrylamide gel containing lauric acid. These subfractions roughly corresponded to HDL2 and HDL3, respectively, which were separated by ultracentrifugation. Nicomol treatment increased the HDL2e/HDL3e ratio as is observed for the HDL2/HDL3 ratio, in addition to the increase in total HDL cholesterol concentration. The electrophoretic determination of HDL2e/HDL3e ratio in combination with HDL cholesterol level seemed to be clinically important in assessment of the alteration of HDL2 and HDL3 under physiological and pathological conditions.     

Einbau von 4-14C-markiertem Cholesterol in die Cholesterol-Ester-Fraktion der Plasma-Lipoproteine bei Lebercirrhotikern

Zusammenfassung Bei 5 Patienten mit gesicherter Lebercirrhose wurden in vivo-Incorporationsstudien mit 4-¹⁴-C-Cholesterol durchgeführt. Alle Patienten wiesen niedrige Gesamtcholesterol-Werte, niedrige Cholesterol-Ester-Konzentrationen und niedrige Aktivitäten für die Lecithin: Cholesterol Acyltransferase auf (LCAT). Das Inkorporationsmuster des injizierten Cholesterols entsprach dem Muster, wie es bei normocholesterinämischen, hypercholesterinämischen und hypertriglyceridämischen Patienten bekannt ist, so daß die Inkorporation offensichtlich unabhängig ist von der Esterkonzentration und der Aktivität der LCAT.Die Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt     

Self-assembly of HDL network on mica

The structure of high-density lipoprotein (HDL) is a subject that continues to attract interest. The goal of this study is to observe the self-assembly construction of HDL on mica using atomic force microscopy (AFM). On mica, HDL was observed to form a honeycomb-like network formation. The narrowest part of the HDL wire was approximately 5.6 nm. HDL can be used in the microcircuitry of electronic devices and is of great interest in the field of nanotechnology.