Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level in patients with multiple sclerosis and evidence of direct synthesis in the brain.

Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated impairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06 microgram/ml (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4 micrograms/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06 +/- 0.02 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of lecithin-cholesterol acyltransferase in normolipidemic and dyslipidemic plasma

Summary Plasma lecithin-cholesterol acyltransferase levels and cholesterol esterification rates have been reported to be different between normolipidemic and dyslipidemic subjects. Since apolipoprotein A-I is the presumed primary physiological activator of lecithin-cholesterol acyltransferase, the distribution of the enzyme among A-I-containing lipoprotein particles and A-I-free plasma in normolipidemic and dyslipidemic subjects was examined. A-I-containing lipoprotein particles with and without apolipoprotein A-II were isolated from plasma by immunoaffinity chromatography, and the lecithin-cholesterol acyltransferase mass in these particles and in the A-I-free plasma was quantified by radioimmunoassay. The plasma lecithin-cholesterol acyltransferase concentration was comparable between normolipidemic men (5.9±1.1 μg/ml,n=15) and women (5.8±1.1 μg/ml,n=19), with 71±8% located in particles without apolipoprotein A-II, 17.6±6% in particles containing A-II, and 12±6% in the A-I-free plasma. In patients with elevated cholesterol (n=12), triglyceride (n=10), and with renal failure (n=15) plasma levels of the enzyme were significantly higher (6.7±1.2, 6.9±1.3, and 6.6±1.3 μg/ml, respectively) (P<0.05). In all three patient groups, a higher proportion of the enzyme (27±12%, 33±12%, and 19±9%) was not apo A-I associated. This phenomenon was also observed in plasma samples after incubation at 37°C. Since the characteristics of lipoproteins differ between native and incubated plasma, and between normolipidemic and dyslipidemic plasma, the increased presence of lecithin-cholesterol acyltransferase in dyslipidemic apolipoprotein A-I-free plasma may be related to differences in lipoprotein composition, and may contribute in part to the reported differences in the plasma cholesterol esterification rate.     

Polymorphisms in the gene coding for cholesteryl ester transfer protein are related to plasma high-density lipoprotein cholesterol and transfer protein activity

1. Cholesteryl ester transfer protein activity may have a physiological effect on high-density lipoprotein levels. 2. We examined restriction fragment length polymorphisms associated with the cholesteryl ester transfer protein gene and the apolipoprotein AI gene in a group of 60 unrelated subjects selected from an initial survey of 5000 subjects on the basis of their high-density lipoprotein levels being high or low at the extremes of the distribution. The activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) were also determined. Analysis by selection of those with a low high-density lipoprotein cholesterol level (less than or equal to 1.1 for males, less than or equal to 1.2 for females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a high-density lipoprotein cholesterol level (less than or equal to 2 mmol/l) gave 17 with 62% B2 alleles. 3. The group with low levels of high-density lipoprotein cholesterol had higher activity of cholesteryl ester transfer protein and significantly elevated triacylglycerol levels when compared with the group with high levels of high-density lipoprotein cholesterol. 4. A further significant finding was the correlation of the MspI restriction fragment length polymorphism detected by the apolipoprotein AI gene with lecithin:cholesterol acyltransferase activity.     

缺血性脑血管病患者血浆卵磷脂-胆固醇酰基转移酶活性与其脂质代谢

背景脂质代谢异常是缺血性脑血管病的危险因素之一.很多研究提出其与体内卵磷脂-胆固醇酰基转移酶活性变化有关.目的观察缺血性脑血管病患者血浆卵磷脂-胆固醇酰基转移酶活性与红细胞膜脂质成分含量变化的关系.设计病例对照(实验组对照,标准对照).单位一所大学医学院附属医院的检验科、急诊室及神经内科.对象2002-03/2003-12青岛大学医学院附属医院急诊神经门诊就诊及住院的脑血管病患者105例,均符合第二届全国脑血管病会议的诊断标准,选择脑动脉硬化患者42例和脑梗死63例构成两个患者组,其中男67例,女38例.同期选择在本院健康查体者65例构成对照组,男36例,女29例.方法采集参与者空腹血8 mL,采用酶学方法检测血浆卵磷脂-胆固醇酰基转移酶活性和血清高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B水平,采用邻苯二甲醛-醋酸硫酸方法测定红细胞膜胆固醇含量,采用化学定量法测定红细胞膜磷脂含量.主要观察指标患者组与对照组卵磷脂-胆固醇酰基转移酶活性变化及红细胞膜脂质成分含量的变化.结果按意向分析处理,105例患者组和65例对照组全部进入结果分析.①卵磷脂-胆固醇酰基转移酶活性脑动脉硬化组和脑梗死组活性变化均明显低于对照组[(2.14±0.72)kat/L,(2.06±0.80)kat/L,(2.61±0.74)kat/L,P＜0.01].②高密度脂蛋白胆固醇与载脂蛋白A1水平脑动脉梗化组与脑梗死组明显低于对照组[(11.32±0.33)mmol/L,(1.37±0.33)g/L,(1.28±0.33)mmol/L,(1.27±0.31)g/L,(1.60±0.43)mmol/L,(1.60±0.43)g/L,(t=2.72～5.01,P＜0.01)].③低密度脂蛋白胆固醇及红细胞胆固醇含量脑动脉硬化组与脑梗死组明显高于对照组[(2.94±0.82)mmol/L,(0.63±0.05)mmol/g,(3.02±0.79)mmol/L,(0.60±0.07)mmol/g,(2.56±0.58)mmol/L,(0.57±0.05)mmol/g,(P＜0.01)].并且卵磷脂-胆固醇酰基转移酶活性分别与高密度脂蛋白胆固醇及载脂蛋白A1呈正相关(r=0.247,P＜0.05;r=0.303,P＜0.01),而与低密度脂蛋白胆固醇和红细胞膜胆固醇呈负相关(r=-0.212,P＜0.05;r=-0.346,P＜0.01).结论缺血性脑血管病患者血浆卵磷脂-胆固醇酰基转移酶活性下降,且并非继发于脑梗死发生后,其活性变化与高密度脂蛋白胆固醇及载脂蛋白A1呈正相关,与低密度脂蛋白胆固醇及红细胞膜胆固醇呈负相关性.     

Cholesteryl ester transfer protein in human brain

Summary The evidence that apolipoproteins are found in the cerebrospinal fluid and low-density lipoprotein receptor is found in the brain suggests that the brain may have an active lipid transport system. In plasma, cholesteryl ester transfer protein mediates the exchange and net transfer of cholesteryl ester and triglycerides among lipoproteins. Cholesteryl ester transfer activity was measured in the cerebrospinal fluid and plasma of ten neurologically normal subjects. Cholesteryl ester transfer activity was readily detectable in cerebrospinal fluid (7.4±13% cholesteryl ester was transferred per 20 μl), and this activity was completely abolished with specific antibody against the plasma cholesteryl ester transfer protein. The concentration of cholesteryl ester transfer activity in the cerebrospinal fluid was about 12% of that found in plasma, whereas the concentration of albumin in cerebrospinal fluid was only about 0.6% of that in plasma, suggesting direct synthesis of cholesteryl ester transfer protein within the brain. Cholesteryl ester transfer activity was found in conditioned medium from human neuroblastoma and neuroglioma cells and sheep choroid plexus. The data suggest that cholesteryl ester transfer protein is synthesized and secreted in the brain. This protein could play an important role in the transport and redistribution of lipids within the central nervous system. Deceased January 1991     

A Caucasian male with very low blood cholesterol and low apoA-II without evidence of atherosclerosis

BACKGROUND: It is well known that a high level of apolipoprotein (apo) A-II can be associated with familial combined hyperlipidaemia, and that high apolipoprotein profiles can contribute to the development of atherosclerosis. The serum lipoprotein/apolipoprotein profile of a Caucasian patient who had unusually low serum total cholesterol (83 mg dL(-1)) and triglyceride (28 mg dL(-1)) levels despite a high body mass index (33.5 kg m(-2)), is the subject of this report. MATERIALS AND METHODS: Each lipoprotein was isolated from serum by sequential ultracentrifugation, and serum and lipoprotein lipids and proteins were determined. The cholesteryl ester (CE) conversion ability of lecithin:cholesterol acyltransferase and CE transfer activity of CE transfer protein were assayed, and the composition of apolipoprotein and lipoprotein(-1) was analyzed by electrophoresis and Western blot analysis. RESULTS: Electrophoresis and immunodetection analyses revealed a 60% decrease in the apoA-II band intensity compared to normal reference serum. The decreased apoA-II was associated with reduced very low density lipoprotein-cholesterol and protein content, as well as a greater high-density lipoprotein (HDL)(2) size with high cholesterol content. The CE conversion activity and CE transfer activity of HDL(3) were almost totally lacking in the hypolipidaemic serum, although the expression level of lecithin:cholesterol acyltransferase was normal. Electron microscopy revealed that the obese patient had larger HDL(2) and HDL(3) particle sizes than those of reference serum. CONCLUSION: These results suggest that a decreased apoA-II protein in serum and increased HDL-cholesterol and particle size might protect against hyperlipidaemia and the atherosclerotic process, even in a patient with severe obesity.     

Determination of serum angiotensin-converting enzyme in sarcoidosis

Summary Serum angiotensin-converting enzyme activity was measured in 72 patients with sarcoidosis and in 50 normal controls by a radiochemical assay. SACE levels were examined with respect to the ‘activity’ of the disease, based on clinical, radiographic and physiological assessment. SACE activity in 34 patients with clinical sarcoidosis (147±44.3 nmol/min/ml) was significantly high (p<0.001) when compared to that of 38 patients who had recovered from sarcoidosis (113.9±26.4 nmol/min/ml) and 50 normal subjects (97.8±21 nmol/min/ml). SACE levels were significantly different (p<0.01) between 15 subjects with ‘active’ disease (173.9±51.9 nmol/min/ml) and those with ‘inactive’ disease (126.1±26.3 nmol/min/ml). It is concluded that there is a strict correlation between SACE levels and ‘activity’ of sarcoidosis if multiple criteria (clinical, radiographic and physiological) are employed.     

A comparison of methods for the immunoassay of serum apolipoprotein B in man

Three assays for serum apolipoprotein B, radioimmunoassay, automated immunoprecipitation and rocket immunoelectrophoresis were compared. The antiserum used was raised against lipoprotein of density 1.040–1.053 g/ml (lipoprotein B). Each of the methods had a high degree of specificity when tested against potential interfering substances.The lowest levels of apolipoprotein B could be measured with radioimmunoassay but this sensitivity entailed the use of high dilutions of serum and resulted in a lower precision. Concentration response curves of lipoprotein B solution and serum were parallel for radioimmunoassay and automated immunoprecipitation but were not for rocket immunoelectrophoresis. Serum apolipoprotein B could be assayed by immunoelectrophoresis, however, if serum calibrated against the protein concentration of lipoprotein B solution by either of the other two methods was used as a secondary standard. Such a secondary serum standard also proved advantageous for all the methods because of the relative stability of the apolipoprotein B content of serum as compared to aqueous solutions of lipoprotein B.The mean apolipoprotein B concentration in 29 normolipaemic subjects aged 20–30 years was 0.84 ± 0.12 g/l (mean ± S.D.) by radioimmunoassay, 0.85 ± 0.11 g/l by automated immunoprecipitation and 0.88 ± 0.11 g/l by rocket immunoelectrophoresis. The correlation between apolipoprotein B levels measured by the three methods was good. The ratio of serum cholesterol to serum apolipoprotein B was unaffected by individual differences in serum cholesterol or triglyceride levels. There was no significant difference between fasting and post-prandial serum apolipoprotein B concentrations.     

Levels of vancomycin in the cerebral interstitial fluid after severe head injury

Objective To evaluate the concentrations of vancomycin in the cerebral interstitial fluid after intravenous administration by multiple boli. Design Prospective non randomized study Setting University hospital general ICU Patients Four patients undergone to craniotomy for evacuation of cerebral posttraumatic hemorrhage, who developed pneumonia 4–7 days from the injury Methods Two microdialysis catheters were placed in each patient: one in the edematous brain surrounding the focal lesion and one in the subcutaneous tissue of abdomen. Levels of vancomycin were measured in serum and in the microdialysates samples. Results Plasmatic concentration of 10–15 μg/ml in the trough level was obtained after four administrations of vancomycin. Levels of vancomycin in the subcutaneous tissue was above minimum inhibitory concentrations in all patients after the second administration. Mean serum/brain ratio was 8%. Cerebral interstitial concentration of vancomycin was never above minimum inhibitory concentrations; its maximum value was 1.2 μg/ml. Conclusions In edematous brain close to a posttraumatic hemorrhage the levels of vancomycin do not differ from that in healthy subjects. At these plasmatic concentrations cerebral interstitial levels of vancomycin were insufficient while subcutaneous interstitial levels were effective for clinical use.     

Lecithin: Cholesterol Acyltransferase Activity and Cholestyramine Resin Therapy in Man

The effect of the bile-acid-sequestering agent cholestyramine on esterification of plasma cholesterol has been studied in vitro. No change in the activity of plasma lecithin: cholesterol acyltransferase was found by either of the two assay methods employed. Similarly the resin did not produce any significant change in the ability of plasma to act as substrate for a given lecithin:cholesterol acyltransferase source. It is concluded that the frequently reported relationship between plasma cholesterol concentration and lecithin:cholesterol acyltransferase activity does not represent cause and effect. Also other variables influenced by bile-acid-sequestering agents, such as hepatic cholesterol synthesis, are unlikely to be major determinants of plasma lecithin: cholesterol acyltransferase activity.     

Normal values for aortic diameters in children and adolescents – assessment in vivo by contrast-enhanced CMR-angiography

Aims

Obese subjects with insulin resistance and hypertension have abnormal aortic elastic function, which may predispose them to the development of left ventricular dysfunction. We hypothesised that obesity, uncomplicated by other cardiovascular risk factors, is independently associated with aortic function.

Methods and results

We used magnetic resonance imaging to measure aortic compliance, distensibility and stiffness index in 27 obese subjects (BMI 33 kg/m²) without insulin resistance and with normal cholesterol and blood pressure, and 12 controls (BMI 23 kg/m²). Obesity was associated with reduced aortic compliance (0.9 ± 0.1 vs. 1.5 ± 0.2 mm²/mmHg in controls, p < 0.02) and distensibility (3.3 ± 0.01 vs. 5.6 ± 0.01 mmHg^-1 × 10^-3, p < 0.02), as well as higher stiffness index (3.4 ± 0.3 vs. 2.1 ± 0.1, p < 0.02). Body mass index and fat mass were negatively correlated with aortic function. Leptin was higher in obesity (8.9 ± 0.6 vs. 4.7 ± 0.6 ng/ml, p < 0.001) and also correlated with aortic measures. In multiple regression models, fat mass, leptin and body mass index were independent predictors of aortic function.

Conclusion

Aortic elastic function is abnormal in obese subjects without other cardiovascular risk factors. These findings highlight the independent importance of obesity in the development of cardiovascular disease.     

A comparison of the effectiveness of open and closed endotracheal suction

Objective To compare the effectiveness of open and closed endotracheal suction in recovering thin and thick secretions in normal and injured lungs during conventional and high frequency ventilation. Design and setting Randomised study in a paediatric intensive care model in the animal research laboratory of a tertiary paediatric hospital. Subjects 16 New Zealand White rabbits. Interventions Anaesthetised animals were intubated with a 3.5-mm endotracheal tube. Simulated thin and thick secretions (iopamidol 2 ml, a watery radio-opaque fluid, and fluorescent mucin 1 ml) were instilled in turn 1 cm below the tube tip through a catheter placed via a tracheostomy. Open or closed suction, randomly assigned, was applied for 6 s at −140 mmHg using a 6-F gauge catheter. Following lung injury with repeated saline lavage the procedure was repeated on conventional and high frequency ventilation. Measurements and results Iopamidol recovery was determined by digitally subtracting the post-contrast and post-suction radiographic images. Mucin recovery was determined by fluorescence assay of the aspirate. In the normal lung similar amounts were recovered by both suction methods. In the lavaged lung closed suction recovered less iopamidol during conventional (22 ± 7.5%) and high frequency ventilation (11 ± 2.4%) than open suction (36 ± 12% and 22 ± 8.1%, respectively). Mucin recovery was less with closed suction during conventional (32 ± 28 μl) and high frequency ventilation (30 ± 31 μl) than with open suction (382 ± 235 μl and 241 ± 153 μl). Conclusions In the injured lung closed suction was less effective than open suction at recovering thin and thick simulated secretions, irrespective of ventilation mode. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was funded by a project grant from the Murdoch Childrens Research Institute and was supported in part by an Australian National Health and Medical Research Council Medical Postgraduate Research Scholarship (D.G.T.).     

Radioreceptor assay of methionine-enkephalin-like substance in human cerebrospinal fluid

A sensitive and simple radioreceptor assay system for measuring methionine(met)-enkephalin-like substance in human cerebrospinal fluid (CSF) was developed using a particulate fraction of rat brain as a receptor preparation and [³H]dihydromorphine as a radiolabeled ligand in the presence of 1 mM ethylenediamine tetraacetate (EDTA) and 2 mM magnesium acetate. Metenkephalin-like substance was purified from CSF by the combination of Sephadex G-10 and SP-Sephadex (H⁺) column chromatographies to be free of sodium and large molecular weight substance such as β-endorphin. The assays were carried out on samples obtained from normal subjects and patients with the disease of the brain or pituitary by lumbar or ventricular puncture. Mean level in samples obtained from normal subjects by lumbar puncture was 2.6 ± 1.0 pmoles/ml.     

Lecithin: cholesterol acyltransferase activity and cholestyramine resin therapy in man.

The effect of the bile-acid-sequestering agent cholestyramine on esterification of plasma cholesterol has been studied in vitro. No change in the activity of plasma lecithin: cholesterol acyltransferase was found by either of the two assay methods employed. Similarly the resin did not produce any significant change in the ability of plasma to act as substrate for a given lecithin:cholesterol acyltransferase source. It is concluded that the frequently reported relationship between plasma cholesterol concentration and lecithin:cholesterol acyltransferase activity does not represent cause and effect. Also other variables influenced by bile-acid-sequestering agents, such as hepatic cholesterol synthesis, are unlikely to be major determinants of plasma lecithin: cholesterol acyltransferase activity.     

Lovastatin ameliorates depressed intraglomerular proteolytic activities in experimental nephrotic syndrome

Lipid abnormalities have been implicated in the pathogenesis of glomerulosclerosis in experimental models of kidney disease. In previous studies it has been shown that Adriamycin-induced nephropathy is associated with reduced activities of glomerular proteinases. This observation led to the hypothesis that reduced proteolytic activities may be responsible for mesangial protein accumulation, which ultimately leads to global sclerosis of the glomerular tuft. The aim of the present study was to investigate whether lovastatin treatment, which prevents progressive glomerulosclerosis in experimental nephrotic syndrome, would also have an effect on glomerular proteinase activities. Adriamycin administration resulted in a persistent nephrotic syndrome with gross proteinuria (377±26 mg/24 h), hypoalbuminemia (2.1±0.12 vs. 2.8±0.02 g/dl), hypercholesterolemia (575±74 vs. 68±1.5 mg/dl) and elevated triglyceride levels (1,155±78 vs. 57±8 mg/dl). Glomerular azocaseinolytic activities both at pH 5.4 (−21%) and 7.4 (−37%) were significantly reduced. In contrast to human subjects, nephrotic rats that were treated with lovastatin displayed reduced triglyceride levels (767±134 mg/dl); their serum cholesterol, however, remained unchanged. In terms of glomerular proteolytic enzyme activities, the decline in azocaseinolysis at both pH values was, at least partly, prevented by lovastatin. On the basis of these data, it appears that the beneficial effect of lovastatin on the evolution of glomerulosclerosis in the nephrotic rat is associated with the conservation of glomerular proteolytic activities.     

基于串联质谱标签技术筛选免疫介导性脱髓鞘疾病诊断与鉴别诊断的生物标志物

目的:采用串联质谱标签（TMT）联合液相色谱串联质谱（LC-MS/MS）筛选免疫介导性脱髓鞘疾病诊断与鉴别诊断的潜在生物标志物。方法:选择首都医科大学附属北京天坛医院2020年1月至2021年1月收治的20例脱髓鞘疾病患者（脱髓鞘组）,包括10例吉兰-巴雷综合征（GBS）患者（GBS亚组）与10例多发性硬化（MS）患者...     

Cystatin C, alias post-gamma-globulin: a marker for multiple sclerosis?

Cystatin C, alias post-gamma-globulin or gamma-trace protein, has been shown to be a potent inhibitor of cysteine proteinases; this protein is normally present in different biological fluids, but particularly so in cerebrospinal fluid. The concentration of cystatin C was determined by radial immunodiffusion in cerebrospinal fluid from patients affected with multiple sclerosis, patients affected with various neurological diseases and in controls; it was also determined in brain tissue from 2 patients affected with multiple sclerosis and 3 control brains. Cystatin C cerebrospinal fluid levels were undetectable or depressed in many multiple sclerosis cases and the median value differed significantly from the control one. Its low concentration in multiple sclerosis suggests that the regulation of cysteine proteinases is impaired in this disease; hence enhanced activity of cysteine proteinases could initiate, or increase the breakdown of myelin. Although it is perhaps a little premature to consider cystatin C as a marker for multiple sclerosis, this protein is nevertheless associated to demyelination; consequently its biochemical assay in cerebrospinal fluid is recommended as a complementary diagnostic tool.     

Altered epitope expression of human interstitial fluid apolipoprotein A-I reduces its ability to activate lecithin cholesterol acyl transferase.

In human peripheral interstitial fluid, esterification of cholesterol by lecithin cholesterol acyltransferase (LCAT) was found to occur at a rate of only 10% of that in plasma (5.6 +/- 1.8 compared with 55.6 +/- 7.8 nmol/ml per h). Measurement of cholesterol esterification in the presence of excess reconstituted apoA-I HDL (rA-I HDL) revealed an LCAT activity in interstitial fluid of 24% of that in plasma, indicating that the low rate of esterification could not be caused by limiting mass of LCAT enzyme. When plasma was diluted to the same concentration as in interstitial fluid, the percent cholesterol esterification rate was the same as undiluted plasma and significantly higher than that of interstitial fluid. These findings led us to postulate that poor activation of LCAT in interstitial fluid may result from a change in conformation in apoA-I. To test this hypothesis, a monoclonal antibody AI-11 that inhibits apoA-I activation of LCAT was used to measure apoA-I in interstitial fluid and plasma. Antibody AI-11 recognized interstitial fluid apoA-I poorly, whereas a polyclonal antibody recognized interstitial fluid apoA-I normally. Incubation of antibody AI-11 with high density lipoprotein or rA-I HDL inhibited apoA-I activation of LCAT. We conclude that the altered conformation of apoA-I in interstitial fluid may render it a poor activator of LCAT.     

血浆卵磷脂-胆固醇酰基转移酶与红细胞膜脂质成分的相关性探讨

目的 探讨缺血性脑血管病(ischemic cerebrovascular disorders,ICVD)患者血浆卵磷脂-胆固醇酰基转移酶(LCAT)活性与红细胞膜脂质成分含量的相关性。方法 采用酶学方法分别测定105例ICVD患者和65例健康对照者血浆LCAT活性,并同时检测血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1和载脂蛋白B(apoA1,apoB)、红细胞膜胆固醇(RBCM-CH)和红细胞膜磷脂(RBCM-PL)含量。结果 ICVD患者LCAT活性、HCL-C及apoA1含量明显低于对照组(P<0.05),LDL-C、apoB、RBCM-CH及RBCM-CH／RBCM-PL比值显著高于对照组(P<0.05),并且LCAT活性分别与HDL-C、及apoA1呈正相关(P<0.01、P<0.05),而与LDL-C和RBCM-CH呈负相关(P<0.05)。结论 ICVD患者脂质代谢方面的异常可能与血浆LCAT活性降低有关。     

Effect of lipoprotein concentration and lecithin: cholesterol acyltransferase activity on cholesterol esterification in human plasma after plasma exchange

The rate of cholesterol esterification in plasma, plasma lecithin cholesterol acyltransferase (LCAT) activity and plasma lipoprotein levels have been measured in five subjects who underwent therapeutic plasma exchange to reduce their plasma cholesterol concentration. In the week following the exchange the cholesterol esterification rate and the plasma triglyceride concentration returned rapidly in parallel to pre-exchange levels, while high density lipoprotein (HDL) cholesterol and LCAT activity returned to normal more slowly but also in parallel. The data suggest that the rate-limiting factor for cholesterol esterification in plasma is unlikely to be solely the enzyme levels, but is probably a combination of factors, including the enzyme level and either substrate availabiltiy or product removal. Plasma very low density lipoprotein (VLDL) may either provide substrates for the reaction or provide a means of removing one of the products from the site of reaction.