High-density Lipoprotein Subfractions Research Articles

Exercise intensity: Its effect on the high-density lipoprotein profile

Objective: To determine the effect of aerobic exercise intensity on the active subfraction of serum high-density lipoprotein (HDL) concentration. Design: A randomized control, before-and-after investigation that tested the hypothesis that high-intensity exercise training would result in improvements in serum concentrations of HDL subfraction 2 (HDL 2) greater than those accompanying moderate-intensity training. Setting: Exercise tests were completed in a hospital stress testing laboratory, and cholesterol analyses were performed in a university research laboratory. Exercise training was performed in the community at a site determined by the subject. Subjects: Subjects were 25 healthy female employees of a teaching hospital. Intervention: Maximum treadmill tests and serum cholesterol profiles were assessed in 25 women before and after a 12-week aerobic walking regimen; 12 women in a high-intensity exercise group (HIG) walked at a target heart rate of 80% and 13 women in a moderate-intensity exercise group (MIG) walked at a heart rate of 60% of their heart rate reserve for a distance of 2 miles three times weekly. Main Outcome Measures: The main dependent variable was HDL 2 other measures of the HDL profile were total HDL and HDL 3. Peak oxygen uptake (V0 2) was also evaluated as a dependent variable to ensure a general aerobic adaptation resulted from the exercise regimen. Measures were analyzed as pretraining to posttraining change scores and absolute values using independent and dependent t tests as appropriate. Statistical significance was assigned at p < .05. Results: Total HDL was 32.3 ± 8.5mg/dL before and 40.3 ± 10.6mg/dL after training in the MIG and 31.6 ± 6.2mg/dL before and 38.2 ± 12.Omg/dL after training in the HIG. HDL 2was 14.2 ± 5.7mg/dL before and 18.5 ± 6.9mg/dL after training in MIG. HDL 2 was 13.0 ± 6.2mg/dL before and 19.6 ± 8.9mg/dL after training in the HIG. Total HDL and HDL 2 increased significantly in both groups as a result of exercise training, and intragroup differences were not observed. HDL 3 was not affected by exercise training. Training resulted in significant increases in peak V0 2 in both MIG and HIG (29.0 ± 5.0 to 31.9 ± 5.4mL/kg/min in the MIG and 30.7 ± 5.2 to 33.5 ± 6.3mL/kg/min in the HIG). Intergroup differences in change scores for peak V0 2, HDL, and HDL 2 were not observed. Conclusion: The results and analyses did not support the hypothesis that the HIG would acquire increases in HDL 2 profile beyond those observed for the MIG. Moderate-intensity training was sufficient to improve the HDL profile, and high-intensity training appeared to be of no further advantage as long as total training volume (total walking distance per week) was constant.

Plasma phospholipid transfer protein activity, high density lipoprotein subfractions and atherogenesis: Studies in mice and man

Plasma phospholipid transfer protein activity, high density lipoprotein subfractions and atherogenesis: Studies in mice and man

Genetic variations of lipoprotein lipase and hepatic triglyceride lipase and their influence to low density and high density lipoprotein subfractions

Genetic variations of lipoprotein lipase and hepatic triglyceride lipase and their influence to low density and high density lipoprotein subfractions

Clinical significance of plasma HDL subfractions (HDL 2, HDL 3) in patients with peripheral arterial disease (PAD) in the Greek population

Objective: In this study the major high density lipoprotein (HDL) subfractions (HDL 2, HDL 3) were examined, in angiographically selected patients with peripheral arterial disease (PAD). Results: Patients with PAD have significantly high triglyceride levels. HDL 2 and HDL 3 levels were found significantly reduced in patients with PAD. Also, the ratio HDL 2-C/HDL 3-C was significantly reduced in patients with PAD. Conclusions: The aim of the present study is to provide additional support to the hypothesis that the determination of HDL subfractions could be useful to elucidate possible mechanism(s) for a better assessment of the risk profile for PAD.

The Effect of Insulin Delivery Route on Lipoproteins in Type I Diabetic Patients on CAPD

To evaluate the influence of subcutaneous and intraperitoneal (i.p.) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). A before-after trial. University hospital outpatient care. Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 +/- 2.9 (SEM) years and duration of diabetes 31.4 +/- 3.4 years. Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with i.p. insulin. The studies were performed after a median time of 3 months on each treatment. Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. After changing from subcutaneous insulin to i.p. insulin, plasma HDL cholesterol decreased (from 1.29 +/- 0.13 mmol/L to 0.96 +/- 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased (p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 (p < 0.01). ApoA-I (p < 0.05) decreased while the ApoB/ApoA-I ratio (p < 0.01) and the ApoA-I/HDL-cholesterol ratio (p < 0.01) increased during i.p. insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin (p < 0.01). In diabetic patients on CAPD therapy, i.p. insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

A new extended-release niacin (niaspan): efficacy, tolerability, and safety in hypercholesterolemic patients

Immediate-release niacin manifests beneficial effects in cardiovascular disease with respect to dyslipidemic states. It lowers low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein(a), and apoprotein B; at the same time, it increases high-density lipoprotein (HDL) cholesterol, HDL 2, and apoprotein A-I. However, use of crystalline niacin has drawbacks: therapy requires multidose regimens, and side effects include flushing and pruritus. Slowing absorption with sustained-release formulations succeeds in decreasing flushing and increasing tolerance, but increases in hepatic enzyme levels have raised safety concerns. A new extended-release, once-daily formulation of niacin (Niaspan) shows promise in minimizing flushing while avoiding hepatotoxicity. A multicenter, randomized, double-blind clinical trial of Niaspan enrolled 122 patients with confirmed diagnosis of primary dyslipidemia (LDL cholesterol >4.14 mmol/L [160 mg/dL] and triglycerides <9 mmol/L [800 mg/dL]) into 3 treatment groups: (1) Niaspan 1,000 mg/day; (2) Niaspan 2,000 mg/day; and (3) placebo. The primary treatment endpoint was LDL-cholesterol level. This endpoint was not significantly affected by placebo (0.2% increase), but Niaspan decreased LDL cholesterol by 5.8% (1,000 mg/day) and 14.6% (2,000 mg/day) (p <0.001). Likewise, with placebo there were significant changes in total cholesterol, triglycerides, lipoprotein(a), and apoprotein B, whereas both Niaspan 1,000 and 2,000 mg/day significantly (p <0.001) decreased these parameters. In addition, both Niaspan groups showed significant (p <0.001) increases in HDL cholesterol (17% and 23%, respectively), including HDL subfractions. With respect to flushing, 20% of the placebo group reported at least 1 episode, whereas 88% and 83% of the Niaspan 1,000- and 2,000-mg/day groups, respectively, reported episodes. There was no hepatotoxicity as liver enzyme levels remained within clinically accepted limits in all treatment groups. However, Niaspan 2,000 mg/day showed a significant increase in aspartate aminotransferase compared with baseline and placebo. This trial demonstrated a cholesterol-modifying effect of Niaspan consistent with those reported for niacin, but demonstrated a better tolerance for flushing. Moreover, in contrast to sustained-release formulations, Niaspan showed relatively mild hepatic effects.

Mechanism of high-density lipoprotein subfractions inhibiting copper-catalyzed oxidation of low-density lipoprotein

Objective: To investigate the role of HDL subfractions, HDL 2 and HDL 3, on the oxidation of LDL catalyzed by 5 μM Cu 2+ ion, and to illustrate the mechanism of the generation of conjugated diene and thiobarbituric acid reactive substances (TBARS) during LDL oxidation. Methods: LDL was incubated for 8 h with 5 μM Cu 2+ ion in phosphate-buffered saline (PBS) alone, or in the presence of HDL 2, HDL 3, HSA, BSA, or transferrin. Meantime, LDL was incubated for 24 h with 10 μM Ni 2+ ions in PBS. The amount of conjugated diene and TBARS in each sample of LDL were measured. Results: (a) HDL 2 and HDL 3 could inhibit the generation of conjugated diene, but could not inhibit the generation of TBARS; (b) the transferrin containing HDL 3 shows the ability of inhibiting the generation of both conjugated diene and TBARS; (c) the transferrin presented in blood exhibits the inhibitory effect on the generation of conjugated diene and TBARS, however, when the transferrin is saturated with Fe 3+ ion, it could not inhibit the generation of TBARS; (d) HSA and BSA could prevent the generation of conjugated diene and TBARS; (e) Ni 2+ ion could induce the generation of conjugated diene, but the amount of TBARS was much smaller than that induced by Cu 2+ ion. Conclusion: HDL 2 and HDL 3 play important role in the copper-catalyzed oxidation of LDL; it is absolutely necessary to require chelation of Cu 2+ ion for inhibiting generation of TBARS; whereas, inhibition of conjugated diene can be fulfilled either by chelating Cu 2+ ion, or the free radicals scavenger.

Factors influencing the ability of HDL to inhibit expression of vascular cell adhesion molecule-1 in endothelial cells.

We have previously reported that high density lipoproteins (HDLs) inhibit the cytokine-induced expression of adhesion molecules in endothelial cells. Here we investigate whether different preparations of HDLs vary in their ability to inhibit the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) activated by tumor necrosis factor-alpha (TNF-alpha). HDLs collected from a number of different human subjects all inhibited VCAM-1 expression in a concentration-dependent manner, although the extent of inhibition varied widely between subjects. The inhibitory activities of the HDL2 and HDL3 subfractions isolated from individual subjects also differed. Whether equated for concentrations of apolipoprotein (apo) A-I or cholesterol, the inhibitory activity of HDL3 was superior to that of HDL2. This difference remained apparent even when the HDL subfractions were present only during preincubations with the HUVECs and were removed before activation by TNF-alpha. To determine whether the inhibitory effect of HDL3 was influenced by apolipoprotein composition, preparations of HDL3 were modified by replacing all of their apo A-I with apo A-II. This change in apolipoprotein composition had no effect on the ability of the HDL3 to inhibit endothelial VCAM-1 expression. Thus, it has been shown that different preparations of HDLs differ markedly in their abilities to inhibit VCAM-1 expression in cytokine-activated HUVECs. The mechanism underlying the differences remains to be determined.

Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery.

The morbidly obese have a disproportionately greater risk of hypertension, diabetes, and coronary artery disease than their lean or less seriously obese counterparts. Roux-en-Y gastric bypass surgery has been found to be highly effective in inducing, and sustaining, weight loss in individuals with morbid obesity. The purpose of the present study was to examine the effects of weight loss with Roux-en-Y gastric bypass surgery (GBP) on blood pressure, fasting blood glucose, and the lipid/lipoprotein status of 61 morbidly obese women and 21 men. Anthropometric and blood pressure assessments and blood samples for glucose and lipid/lipoprotein analyses were obtained before surgery and at 6 to 12 months postoperatively. By this time, morbidly obese (MO) males and females had lost 33% and 30% of their initial body weight, respectively, along with significant reductions in fasting blood glucose (p < 0.01) and systemic blood pressure (p < 0.05). Weight loss with GBP was also associated with significant reductions in the apoprotein B-containing lipoproteins and the triglyceride and cholesterol composition of these particles. There was a trend (p < 0.10) toward increased serum levels of high density lipoprotein (HDL)-cholesterol following GBP, and significant (p < 0.05) improvement in HDL subfraction distribution and composition. These findings demonstrate the effectiveness of GBP in inducing metabolic changes in the MO population, which may reduce the risk of coronary artery disease, diabetes, and hypertension.

Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein.

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein

Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein

Evidence against alterations in Lecithin:cholesterol acyltransferase (LCAT) activity in familial combined hyperlipidemia.

Elevated concentrations of plasma cholesterol and triglycerides are characteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by converting unesterified cholesterol to cholesterol ester in the process of maturation of HDL in the presence of its activator, apolipoprotein (apo) A-I. We hypothesised that alterations in LCAT activity or plasma concentrations or gene sequence of apo A-I could influence HDL metabolism in these patients. We studied cholesterol concentrations of high density lipoprotein subfractions and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p=0.018) and HDL2 (p=0.008) were significantly decreased in the FCHL group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p=0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the FCHL group (p <0.0001), the latter suggesting the existence of compositional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94+/-3.95 nmol/ml per h) and control (20.13+/-6.86 nmol/ml per h) groups showed no statistically significant differences. A significant positive correlation of LCAT activity with total HDL (r=0.42), HDL3 cholesterol (r=0.46) and apolipoprotein A-I (r=0.47) was observed in affected subjects but not in controls. An association between a Ga(-75)-A variation in the promoter region of the apo A-I gene and elevated concentrations of apo A-I (p=0.009) and apo C-III (p=0.041) was observed. This association was strongly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCHL. Our data suggests that LCAT activity is normal in FCHL and, therefore, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction.

Changes in plasma lipids and lipoproteins in humans during a 2-year period of dietary restriction in Biosphere 2.

A cohort study was performed of 8 people sealed inside Biosphere 2 to evaluate the effects of dietary restriction in humans on lipid and lipoprotein levels and the relationship of these levels to energy, fat, and protein content of the diet, and body weight, weight change, and energy expenditure. Eight healthy people aged 27 to 67 years, 4 women and 4 men, were sealed inside Biosphere 2 from September 26, 1991, to September 26, 1993, the longest sustained period in an "isolated confined environment" on record. They were studied throughout confinement and for more than 2 years after their exit and return to an ad libitum diet. Food available was severely restricted during most of the 2-year period inside Biosphere 2. High work output was maintained and food quality remained high, resulting in prolonged restriction of energy intake without malnutrition. Fasting plasma cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels; HDL subfraction distribution; dietary energy, fat, and protein content intake; and height, weight, weight change, and energy expenditure were measured. Total plasma cholesterol and triglyceride levels decreased 30% and 45%, respectively. The HDL and low-density lipoprotein levels also decreased and, in some participants, levels of HDL2 subfractions were increased. Multivariate analysis showed that the major cause of these changes was energy restriction. Energy restriction was the major factor leading to low lipid and lipoprotein levels. Energy restriction with adequate nutrition of young and middle-aged people may substantially reduce risk for atherosclerosis and consequent coronary artery and cerebrovascular disease.

Cholesterol transport between cells and high density lipoprotein subfractions from obese and lean subjects

We studied the pathway of cholesterol efflux from fibroblasts by testing plasma samples from obese and lean subjects. Plasma samples were incubated with [3H]cholesterol-labeled human skin fibroblasts for 1 h to ensure uniform labeling of all of the high density lipoprotein (HDL) subfractions. Supernatants were then transferred to unlabeled cells and the displacement of labeled cholesterol within HDL subfractions by unlabeled cellular cholesterol was analyzed in short-term experiments. Plasma samples of obese subjects were characterized by a lower content of total apolipoprotein A-I (apoA-I) and α1-HDL and a lower overall capacity to take up labeled cholesterol. In plasma of lean subjects, preβ2-HDL and α1-HDL appeared to be the most active particles in the initial uptake of unlabeled cellular cholesterol. By contrast, in plasmas of obese subjects, the preβ1-HDL appeared to be most active in taking up unlabeled cellular cholesterol and transferring [3H]cholesterol. There were negative correlations between body mass index (BMI) and apoA-I and α1-HDL concentrations, and with the apparent increments of cellular cholesterol uptake within preβ2-HDL and α1-HDL, as well as with the overall capacity to promote cholesterol efflux. By contrast, BMI was positively correlated with the apparent increment in cellular cholesterol within preβ1-HDL. While cholesterol efflux was correlated with total plasma apoA-1, there were no such correlations with the concentration of any individual HDL subfraction. We conclude that the pattern of cholesterol transfer between fibroblasts and high density lipoprotein particles is influenced by body fatness and may be a factor in the abnormal metabolism of HDL in obesity.—Sasahara, T., P. Nestel, N. Fidge, and D. Sviridov. Cholesterol transport between cells and high density lipoprotein subfractions from obese and lean subjects.

The effects of cholesterol uptake from high-density lipoprotein subfractions on biliary sterol secretion in rats with essential fatty-acid deficiency.

High-density lipoprotein (HDL) participates in the transfer of cholesterol to the liver, in which it is subsequently excreted into bile as bile acid and cholesterol. In this study, the effect of essential fatty-acid (EFA) deficiency on cholesterol contribution from HDL subfractions to bile was investigated. Rats that were rendered EFA-deficient over 4 weeks displayed changes in their plasma HDL subfractions and liver tissue fatty acids. Plasma linoleic (18:2n6), linolenic (18:3n3,) and arachidonic (20:4n6) acids decreased, whereas palmitoleic (16:1n7) and eicosatrienoic (20:3n9) acids increased. EFA deficiency was confirmed by an elevation of the 20:3(n-9)/20:4(n-6) index. To examine the hepatic handling of lipoprotein-derived cholesterol, HDL2 and HDL3 from donor rats were isolated, labeled with [14C]-cholesterol, and injected iv into EFA-deficient and normal rats with a bile fistula. In HDL subfractions from control rats, no significant variations were noted in the specific activity of cholesterol output in both groups of EFA recipient rats; however, the output of biliary bile acids was significantly decreased in EFA-deficient rats following the administration of labeled HDL3. In HDL2 and HDL3 originating from EFA-deficient rats, a decrease in the specific activity of both biliary cholesterol and bile acid output was recorded in EFA-deficient rats. Concomitant with the defective HDL2- and HDL3-[14C] cholesterol translocation into bile of EFA-deficient rats, increased hepatic very-low-density lipoprotein (VLDL)-[14C] cholesterol secretion was observed in vivo. HDL2 and HDL3 particles, derived from EFA-deficient rats, had an altered composition including a depletion in apo A-I and an enrichment in apo E isoforms, which are the the two major HDL apolipoproteins involved in the delivery of cholesterol to the liver. Taken together, these results show that normal EFA status is necessary for efficient HDL-cholesterol processing by the liver.

Receptor binding of an apolipoprotein E-rich subfraction of high density lipoprotein to rat and human brain membranes

During nerve cell degeneration, cholesterol released from the degrading cells is conserved through the formation of a cholesterol–apolipoprotein (apo) E complex which is subsequently taken up by regenerating nerve cells. The aim of the present project was to identify the physiologically relevant lipoprotein receptor for this lipoprotein complex which has remained elusive. HDL was separated into apo E-rich and apo E-poor subfractions and labelled with [ 14C]-sucrose. Labelled apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration-dependent manner and was a saturable process. Essentially no binding occurred with [ 14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by low density lipoprotein (LDL) and by α 2-macroglobulin. These results provide new evidence that native apoE-rich HDL particles resembling those present in the brain bind to rat brain membranes and that the binding may be due, at least in part, to the LDL receptor and to the LDL-receptor related protein. Evidence was also provided for the presence of a receptor which binds [ 14C]-sucrose human apoE-rich HDL in human brain. Characterisation of the receptor which mediates the uptake of cholesterol from HDL-like complexes by brain cells is important in understanding the role of apoE in the central nervous system and of the alterations which occur in disorders such as Alzheimer's disease.

Effects of acute exercise on high density lipoprotein cholesterol and high density lipoprotein subfractions in moderately trained females.

Increases in high density lipoprotein cholesterol (HDL-C) levels have previously been reported after moderate exercise bouts lasting less than two hours in men. Little information exists, however, on HDL-C responses...

Novel large apolipoprotein E-containing lipoproteins of density 1.006-1.060 g/ml in human cerebrospinal fluid.

Although the critical role of apolipoprotein E (apoE) allelic variation in Alzheimer's disease and in the outcome of CNS injury is now recognized, the functions of apoE in the CNS remain obscure, particularly with regard to lipid metabolism. We used density gradient ultracentrifugation to identify apoE-containing lipoproteins in human CSF. CSF apoE lipoproteins, previously identified only in the 1.063-1.21 g/ml density range, were also demonstrated in the 1.006-1.060 g/ml density range. Plasma lipoproteins in this density range include low-density lipoprotein and high-density lipoprotein (HDL) subfraction 1 (HDL1). The novel CSF apoE lipoproteins are designated HDL1. No immunoreactive apolipoprotein A-I (apo A-I) or B could be identified in the CSF HDL1 fractions. Large lipoproteins 18.3 +/- 6.6 nm in diameter (mean +/- SD) in the HDL1 density range were demonstrated by electron microscopy. Following fast protein liquid chromatography of CSF at physiologic ionic strength, apoE was demonstrated in particles of average size greater than particles containing apoA-I. The largest lipoproteins separated by this technique contained apoE without apoA-I. Thus, the presence of large apoE-containing lipoproteins was confirmed without ultracentrifugation. Interconversion between the more abundant smaller apoE-HDL subfractions 2 and 3 and the novel larger apoE-HDL1 is postulated to mediate a role in cholesterol redistribution in brain.

Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins

Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes. Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL. The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05). Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Effects of Treatment of Secondary Hyperparathyroidism on the Lipid Profile in Patients on Hemodialysis

Abnormalities in circulating lipoprotein concentrations are a characteristic finding in patients undergoing dialytic therapy. A substantial number of these patients display type IV hyperlipoproteinemia. Certain data suggest that secondary hyperparathyroidism may induce disturbances in lipid metabolism. To evaluate the effects of pulse calcitriol therapy on the lipid profile in these patients, we undertook a prospective study in 12 patients on stable bicarbonate hemodialysis. Lipid parameters comprising cholesterol and the low- as well as the high-density lipoprotein subfractions, triglycerides, apolipoproteins A and B, serum parathyroid hormones (iPTH), alkaline phosphatase, calcium, phosphorus, hematocrit, and blood urea were obtained prior to commencement of pulse calcitriol therapy and again 8–10 weeks later. Calcitriol therapy was associated with a decrease in serum iPTH levels (701 ± 103.9 vs. 220.3 ± 50.5 pmol/l; p < 0.001). Significant increases in high-density lipoprotein cholesterol (32.8 ± 2.7 vs. 38.8 ± 2.3 mmol/l; p < 0.05) and apolipoprotein A-I (107.8 ± 6.1 vs. 121.8 ± 5.8 g/l; p < 0.05) were noted during the course of the study. Moreover, serum iPTH correlated inversely with high-density lipoprotein cholesterol and apolipoprotein A-I. There were no changes in other lipid parameters except for low-density lipoprotein cholesterol which showed a tendency to increase. We conclude that in short-term study, pulse oral calcitriol therapy is associated with an improvement in the lipid profile in patients with secondary hyperparathyroidism. However, it remains to be established whether ameliorating the uremic dyslipidemia results in any long-term clinical benefits.