Studies on the apolipoproteins and lipoproteins of cord serum

Studies on the cord serum lipid transport system were initiated to determine whether there is a correlation between decreased cord serum lipid levels and the absence or diminished level of some or all of the human serum apolipoproteins. Immunologic studies indicated the presence of all the well-characterized apolipoproteins and provided evidence that these apolipoproteins occurred primarily as distinct lipoprotein species with a paucity of association complexes or what others have termed "triglyceride-rich" lipoproteins. Quantitation of the apolipoproteins present in cord serum by electroimmunoassay yielded the following mean levels: A-I = 73O mg/liter; A-II = 410 mg/liter; apolipoprotein B = 280 mg/liter; C-I = 59 mg/liter; C-II = 32 mg/liter; C-III = 65 mg/liter; apolipoprotein D = 37 mg/liter; and apolipoprotein E = 85 mg/liter. Levels of C-I, C-II, and apolipoprotein E approached adult levels (83 to 86% of the adult levels), whereas apolipoproteins B and D were most reduced when compared to the adult concentrations, 29 and 37%, respectively. The three other apolipoproteins were present at approximately one-half the levels found in adults.     

Plasma apolipoprotein profiles of male and female rats

To determine if sex differences exist in the apolipoprotein profile of the rat, the concentrations of the major apolipoproteins and lipids of 12-week-old male and female rats were measured in the plasma as well as in the individual lipoprotein fractions. Plasma apo B, triglyceride, and cholesterol concentrations were significantly higher in male rats than in female rats. Plasma concentrations of apo A-I, apo E, apo A-IV, and apo C-III did not differ between the sexes. Male rats had higher concentrations of apo B in the very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and the low density lipoproteins (LDL). These results further support the evidence that sex hormones influence lipoprotein metabolism in the rat.     

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.     

Psychological and socio-medical aspects of HIV/AIDS: a reflection on publications in AIDS care (1989-1995)

Cardiovascular disease is the leading cause of death in non-insulin dependent diabetes mellitus and first degree relatives of such patients are at increased risk of developing diabetes and cardiovascular disease. The aim of the present study was to determine whether lipid abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients. Cholesterol, triglycerides, apolipoprotein A-I and apolipoprotein B concentrations were measured in serum; the lipoprotein fractions very low density, intermediate density, low density and high density lipoprotein were prepared by sequential flotation ultracentrifugation and their composition investigated. The groups were matched for age, sex and blood glucose concentrations although the relatives (n = 126) were more insulin resistant as determined using the homeostasis model assessment method [1.9 (0.8-9.0) vs 1.6 (0.4-4.9) mmol/mU per l (mean [95% confidence intervals]); p < 0.001] and had greater body mass indices [26.6 (4.1) vs 24.8 (3.9) (mean [S.D.]); p = 0.001] than control subjects (n = 126). Relatives had higher serum apolipoprotein B concentrations than control subjects [0.9 (0.3) vs 0.8 (0.3) g/l, p = 0.02) and lower serum apolipoprotein A-I concentrations (1.4 (0.3) vs 1.5 (0.3), p = 0.02). In multivariate linear regression analysis of all subjects log insulin resistance (p = 0.0001), age (p = 0.002) and waist:hip ratio (p = 0.01) were independent predicators of apolipoprotein B concentrations while waist:hip ratio (p < 0.001) and smoking status (p = 0.002) were independent predictors of apolipoprotein A-I concentrations. Lipoprotein composition (measured in a subgroup of 76 control subjects and 88 relatives), serum cholesterol and serum triglyceride concentrations did not differ between the groups. We conclude that atherogenic apolipoprotein abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients.     

Abnormal activation of lipoprotein lipase by non-equilibrating apoC-II: further evidence for the presence of non-equilibrating pools of apolipoproteins C-II and C-III in plasma lipoproteins

Using artificial triglyceride emulsions, we have demonstrated the presence of non-equilibrating pools of apolipoproteins C-II and C-III in human plasma lipoproteins. As the concentrations of acceptor triglycerides were increased, a greater fraction of both apoC-II and apoC-III shifted away from the native plasma lipoproteins to the artificial lipid emulsions. All of the apoC-II and apoC-III in very low density and high density lipoproteins (VLDL and HDL), however, could not be removed from native plasma lipoproteins. The percent of total plasma apoC-II and apoC-III that could be recovered in the VLDL and HDL density fractions varied when plasma from different individuals was used. When plasma samples from normotriglyceridemic subjects were used, HDL was the primary donor of apoCs. The percent of total plasma apoCs associated with HDL decreased from 60% to 25% for apoC-II and from 65% to 15% for apoC-III. When plasma samples from hypertriglyceridemic subjects were incubated with artificial lipid emulsions, VLDL was the primary donor of apoCs. HDL from hypertriglyceridemic subjects only accounted for 5-10% of total fasting plasma apoCs and did not contribute significantly to the final apoC contents of the artificial triglyceride emulsions. To evaluate the significance of the depletion of exchangeable apoCs from plasma HDL, we also examined the ability of control and apoC-depleted HDL to serve as activator for bovine milk lipoprotein lipase (LPL) in vitro. When HDL depleted of exchangeable apoCs were used as the source of plasma apolipoproteins for the activation of LPL in vitro, only 5-10% of the maximal activity obtained with native HDL was demonstrated. In fact, in the presence of comparable concentrations of HDL apoC-II, activation of LPL was the least with HDL which lacked exchangeable apoCs. Our data thus indicated that the presence of exchangeable apoC-II on HDL is necessary for the activation of LPL in vitro. This finding is consistent with our data that suggest that HDL from hypertriglyceridemic subjects do not stimulate LPL as well as HDL from normolipidemic subjects.     

Apolipoprotein A-I complexed with phospholipid promotes hepatic lipoprotein and apolipoprotein secretion in the perfused hamster liver

BACKGROUND: Apolipoprotein A-I within high density lipoprotein (HDL) plays a significant role in the process of reverse cholesterol transport from peripheral tissues to the liver. However, additional roles are not well defined for it in hepatic cholesterol metabolism. We have previously shown in the hamster that dietary cholesterol supplementation resulted in enhancement of apolipoprotein A-I (Apo A-I) in secreted nascent hepatic very low density lipoprotein (VLDL), suggesting that apolipoprotein A-I itself may play a role in hepatic lipoprotein secretion. METHODS: Using the isolated hamster liver with Apolipoprotein A-I perfusion, we then examined the hypothesis that Apo A-I alone or in association with phosphotidylcholine (PC) i.e., Apo A-I/PC as a HDL-like particle, has effects upon hepatic lipoprotein and bile secretion. Ultracentrifugation was performed on perfusate samples at 3 hours on control vs treated livers (Apo A-I/PC, Apo A-I, or PC) to access lipid and protein concentration in VLDL, low density lipoprotein (LDL) and HDL. Four to thirty percent gradient SDS polyacrylamide electrophoresis (PAGE) and Western blot analysis were used on delipidated lipoprotein fractions and microsomes to assess apolipoproteins Apo B, A-I, II, and E. RESULTS: We found that perfusion of reconstituted HDL vesicles containing human apolipoprotein A-I and PC (Apo A-I/PC) 10 mg and 10 mg, respectively, in 22 mL for 3 hours into isolated hamster liver increased cholesterol (CH) and triglyceride (TG) components in secreted HDL; 45- and 6-fold, and in LDL; 15- and 2-fold, respectively. No significant changes occurred in VLDL or in biliary lipids. Concomitantly, Apo A-I/PC perfusion increased Apo E and Apo A-II and HDL and Apo B in LDL, while Apo E decreased in VLDL. Apo A-I/PC perfusion did not change the apolipoprotein content of hepatic microsomes of the perfused liver. Perfusion of apolipoprotein A-I (without PC) or PC (without apolipoprotein A-I) had none of these effects. CONCLUSION: These results indicate that the perfused discoidal apolipoprotein A-I/PC particle affects hepatic lipoprotein assembly and secretion, whereby both lipid and apolipoprotein components are enhanced in secreted HDL and LDL of hepatic origin.     

An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III

An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P less than 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.     

Precipitation procedures used to isolate high density lipoprotein with particular reference to effects on apo A-I-only particles and lipoprotein(a)

Analysis of high density lipoprotein (HDL) isolated from serum without major hypertriglyceridaemia and by five different precipitation methods showed that there were no significant differences in total cholesterol and triglyceride concentrations in the HDL supernatants prepared by the different methods but that free cholesterol, phospholipid, apolipoprotein (apo) A-I and HDL particles containing apo A-I but not apo A-II (LpAI) concentrations were significantly lower for heparin-manganese chloride method 2 (final manganese chloride concentration 92 mmol/l) compared with the other methods. Modest differences in HDL cholesterol, apo A-I and LpAI were observed between heparin-manganese chloride method 1 (final magnesium concentration 46 mmol/l) and the dextran sulphate, phosphotungstate and polyethylene glycol 6000 methods. Lipoprotein(a) (Lp(a)) and apo B were undetectable in the HDL supernatants, indicating that apo B-containing lipoproteins including Lp(a) were essentially completely removed by all the precipitation procedures.     

Familial combined hyperlipidemia: detection and characterisation of the hyperlipidemic profile among children and adolescents

BACKGROUND: Familial combined hyperlipidemia is the commonest genetic form of hyperlipidemia among survivors of myocardial infarction and, therefore, its early detection is crucial for the prevention of coronary artery disease. The aim of the study was to establish the prevalence of hyperlipidemia in the offspring of affected families and to characterize their lipid, lipoprotein and apolipoprotein profile. PATIENT AND METHODS: Forty five subjects below the age of 19 were studied from which 30 were from affected families and 15 from healthy control families. Cholesterol and triglycerides in plasma, VLDL, IDL, LDL and HDL as well as apolipoproteins AI, B, C-II and C-III were measured. RESULTS: Hyperlipidemia was detected in 13 children (43%) from affected families. They also presented significantly elevated concentrations of cholesterol in plasma (p < 0.0001), LDL (p < 0.0001) and HDL (p < 0.05); triglycerides in plasma (p < 0.007), VLDL (p < 0.05) and LDL (p < 0.008), together with significantly increased concentrations of apolipoproteins AI (p < 0.02), B (p < 0.0004), C-II (p < 0.0005) and C-III (p < 0.03). No changes were observed in the IDL fraction. CONCLUSIONS: There is an elevated prevalence of hyperlipidemia among the offspring of patients with familial combined hyperlipidemia. On the contrary to that observed in adults, no alterations of the IDL fraction are present among affected children.     

Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice

The peroxisome proliferator-activated receptor-alpha (PPARalpha) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPARalpha activators have been identified such as fatty acids and steroids. The latter finding and the fact that PPARalpha modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPARalpha in lipid metabolism. This was investigated in the PPARalpha-deficient mouse model. Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPARalpha-deficient mice are significantly higher compared with wild-type controls. Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPARalpha-deficient mice. Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with untreated controls. In contrast, PPARalpha-deficient mice were unaffected by Wy 14,643 treatment. These studies demonstrate that PPARalpha modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate-induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPARalpha.     

African American-white differences in lipids, lipoproteins, and apolipoproteins, by educational attainment, among middle-aged adults: the Atherosclerosis Risk in Communities Study

Measures of socioeconomic status have been shown to be related positively to levels of high density lipoprotein (HDL) cholesterol in white men and women and negatively in African American men. However, there is little information regarding the association between educational attainment and HDL fractions or apolipoproteins. The authors examined these associations in 9,407 white and 2,664 African American men and women aged 45-64 years who participated in the Atherosclerosis Risk in Communities Study baseline survey, and they found racial differences. A positive association for HDL cholesterol, its fractions HDL2 and HDL3 cholesterol, and its associated apolipoprotein A-I was found in white men and white women, but a negative association was found in African American men, and there was no association in African American women. In whites, there was also an inverse association of low density lipoprotein (LDL) cholesterol and apolipoprotein B with educational attainment. With the exception of African American men, advanced education was associated with a more favorable cardiovascular lipid profile, which was strongest in white women. Racial differences in total cholesterol (women only), plasma triglycerides, LDL cholesterol, apolipoprotein B (women only), HDL cholesterol, HDL2 and HDL3 cholesterol, and apolipoprotein A-I were reduced at higher levels of educational attainment. Apart from triglycerides in men and HDL3 cholesterol in women, these African American-white lipid differences associated with educational attainment remained statistically significant after multivariable adjustment for lifestyle factors. Lipoprotein(a) showed no association with educational attainment. These findings confirm African American-white differences in lipids, lipoproteins, and apolipoproteins across levels of educational attainment that were not explained by conventional nondietary lifestyle variables. Understanding these differences associated with educational attainment will assist in identifying measures aimed at prevention of cardiovascular disease.     

Serum concentrations of apolipoproteins in patients with thyroid dysfunction

We measured serum concentrations of apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) in patients with thyroid disease (hyperthyroidism; n = 44, hypothyroidism; n = 15) and in normal subjects (n = 89). We found that apoA-II, B and C-III concentrations revealed significant difference among three groups of the normal (apoA-II; 31.4 +/- 4.9 mg/dl, apoB; 85.8 +/- 16.3 mg/dl, apoCIII; 7.45 +/- 2.99 mg/dl), hyperthyroidism (apoA-II; 29.8 +/- 5.4, apoB; 63.4 +/- 18.9, apoC-III; 6.28 +/- 2.45) and hypothyroidism (apoA-II; 27.5 +/- 5.3, apoB; 108.0 +/- 30.9, apoC-III; 9.43 +/- 2.74). Thyroid hormones showed clear negative correlation to apoB (r = 0.70, p < 0.001). Furthermore, apoC-III was also found to be negatively correlated with thyroid hormone concentrations (r = 0.47, p < 0.001).     

Decreased postprandial high density lipoprotein cholesterol and apolipoproteins A-I and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities

We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.     

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.     

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants

The study purpose was to compare the effect of exercise training on serum lipid and apolipoprotein concentrations and the activities of intravascular enzymes related to lipid transport in previously untrained eumenorrheic, premenopausal (PRM) women (n = 21; mean age, 36 +/- 3 years) and estrogen-free postmenopausal (POM) women (n = 16; mean age, 68 +/- 8 years). Subjects trained at a progressive intensity and duration (50% to 75% maximal O2 consumption [VO2max], 200 to 300 kcal/session) 4 d/wk for 12 weeks. Before and after training, VO2max, body weight, relative body fat, and fasting blood samples were obtained following 2 weeks on a standardized diet designed to maintain body weight and during the early follicular stage for the PRM group. Blood samples were analyzed for serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), the cholesterol content of the HDL3 subfraction, apolipoprotein (apo)A-I and apoB, lipoprotein(a), and the activity of lecithin:cholesterol acyltransferase (LCAT). Total and hepatic triglyceride lipase activity (HTGLA) were determined from plasma samples obtained after heparin administration. The cholesterol content of the low-density lipoprotein (LDL) and HDL2 subfractions and endothelial-bound lipoprotein lipase activity (LPLA) were calculated. A two (group) x two (time) multivariate ANOVA (MANOVA), with repeated measures for time indicated that the exercise-induced changes in physiological measurements, serum lipid or apolipoprotein concentrations, or enzyme activities did not differ between groups. Serum concentrations of TC, LDL-C, and HDL3 cholesterol, TG, and apo A-I and apoB were higher in POM women compared with the PRM group (P < .05 for all). For the combined groups, body weight and relative body fat did not change with training, but VO2max increased an average of 18.5% (P < .05). LPLA, HTGLA, and LCAT activity were unaltered with exercise training. Except for a small but significant decrease in HDL-C (-5.5%) and an elevation in apoB (4.3%; P < .05 for both), the concentrations of serum lipids and apolipoproteins did not change over the training period. We conclude that in previously untrained women, menopausal status does not influence the exercise training response of serum lipids or apolipoproteins or activities of intravascular enzymes related to lipid transport.     

Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.     

Asymmetrical hemispheric activation and behavioral persistence: effects of unilateral muscle contractions

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.     

Influence of different fat emulsions with 10 or 20% MCT/LCT or LCT on lipoproteins in plasma of patients after abdominal surgery

In patients after elective abdominal surgery, different fat emulsions were used to compare their efficacy in total parenteral nutrition and in normalizing plasma lipoprotein levels. In five different groups with 5 patients each, half of the nonprotein calories were given as medium-chain triglycerides/long-chain triglycerides (1:1) or as long-chain triglycerides alone in 10 or 20% fat emulsions or as glucose alone in a control group for 7 days. After surgery, an initial decrease of all plasma lipoprotein components was followed by a different behavior of glyceride-glycerol, cholesterol, phospholipids, and apolipoproteins. Glyceride-glycerol in very-low-density lipoproteins and high-density lipoproteins is increasing during infusion of fat emulsions and decreasing during overnight interruption of infusions. After the 7-day infusion period, there was no significant difference in very-low-density lipoprotein glyceride-glycerol as compared with the values before different infusions. Low-density lipoprotein cholesterol is reaching and exceeding preoperative concentrations between the 4th and the 7th day, most during infusion of 10% fat emulsion and especially due to an increase of free cholesterol. High-density lipoprotein cholesterol and apolipoprotein A-I reach preoperative levels during infusion of fat emulsions but not with glucose alone. Higher than preoperative values are reached in phospholipids with all fat infusions already on day 4. Abnormal lipoprotein X occurred least with the medium-chain/long-chain triglyceride 20% fat-infusion. This fat emulsion is suggested as having the best normalizing effect on plasma lipoproteins and best tolerance in patients after surgery.     

Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition

A very short run time and small sample volumes in the separation of lipoproteins by preparative ultracentrifugation are needed for several investigations. Recently, a very fast sequential separation method was described that needs only 100 min for one run in a centrifugal field of 625,000 x g. We studied the influence of centrifugal fields of this dimension on lipoprotein separation and lipoprotein particle integrity using a Beckman Optima TLX ultracentrifuge with a TLA-120.2 rotor. Rotor speed (120/90/60/30.10(3) rev./min) and run time (100 min/3 h/6.7 h/27 h) were selected in such a way that the product of centrifugal field and run time remained constant. The first conditions correspond to the very fast ultracentrifugation (VFU) procedure with a centrifugal field of 625,000 x g. Thirty different plasma samples covering a wide range of lipid and protein concentrations were separated in the course of two centrifugal runs at densities of 1.006 and 1.063 kg/l which yielded very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and the subnatant of low-density lipoproteins, including high-density lipoproteins (HDL) and concomitant sedimented plasma proteins. The major lipid components of the lipoproteins, triacylglycerols, free and esterified cholesterol, phospholipids and the apolipoproteins B and A-I, were estimated considering the masses of the tube contents after a slicing procedure. Measurements of lipids and proteins showed a very good recovery of better than 94% and 91%, respectively, and precision-within-series (coefficient of variation) of better than 4.2% and 6.5%, respectively. The effects of the rotor speed on the lipoprotein structure appeared to be weak. With increasing rotor speed, VLDL and LDL lipid constituents principally tended to decrease, whereas they increased in the subnatant of the LDL-run. The mean lipoprotein mass composition, considering the mass percentage of each measured particle constituent, did not show significant alterations. Total protein decreased in VLDL and in LDL and increased in the subnatant of the LDL-run. As checked by an enzyme-linked immunosorbent assay (ELISA) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the protein effects were due to nearly complete disappearance of contaminating plasma proteins, especially albumin as the major contamination of VLDL and LDL. The apolipoproteins (apo) B-100, A-I, E and C-I to C-III remained nearly unaffected. The main advantages of VFU were the very short run time (cumulative flotation time is 3.4 h) and the elemination of albumin without repeated runs. The procedure was suitable for the assessment of lipid and protein constituents in lipoproteins from very small plasma samples (500 microliters).     

Effects of one year of treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein a

Lipoprotein a [Lp(a)] has emerged as a critical factor in the assessment of cardiovascular risk. In the study reported here, Lp(a) concentrations were monitored in patients taking pravastatin, a new hydrophilic, HMG-CoA reductase inhibitor. A cohort of patients with frozen plasma aliquots at baseline, week 12 of the double-blind therapy, and week 48 of open-label therapy (1 years' treatment) was selected from 306 participants in a phase 2 dose-ranging study of pravastatin. The 125 men and women in the cohort had mean low-density lipoprotein cholesterol (LDL-C) concentrations of at least 150 mg/dL (3.88 mmol/L), and mean plasma triglyceride concentrations less than 250 mg/dL (2.82 mmol/L) during the baseline diet phase. During the double-blind phase, 46 patients received placebo, and 79 received pravastatin 10, 20, or 40 mg daily. Only the 79 pravastatin-treated patients in the cohort continued in the 48-week open-label study of pravastatin. During the double-blind phase, Lp(a) decreased 4.6% in patients taking placebo, and 0.4% in patients taking pravastatin. Net change was not significant. At week 48, in the patients taking pravastatin, Lp(a) had increased 2.4%, a difference that again was not statistically significant. Low-density lipoprotein cholesterol (-33.6%), total cholesterol (-25.6%), triglycerides (-19.9%), high-density lipoprotein cholesterol (HDL-C) (+7.0%), apolipoprotein A-I (+13.3%), and apolipoprotein B (-33.0%) changed significantly (P < .01). Among 19 patients with baseline Lp(a) levels greater than 30 mg/dL, Lp(a) decreased insignificantly.(ABSTRACT TRUNCATED AT 250 WORDS)