Ten years post-menopausal hormone replacement therapy — Effect on lipoproteins

Serum lipoproteins were measured in 72 post-menopausal women, 40 of whom had been taking the synthetic oestrogen, mestranol, for a period of 10 yr and 32 of whom had been taking identical placebo tablets. Mestranol therapy was found to increase serum triglycerides, decrease low density lipoprotein (LDL) cholesterol and increase high density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was due principally to a marked increase in the cardioprotective HDL₂ fraction. It is concluded that long-term mestranol therapy has a beneficial effect on serum lipoproteins which may help to protect post-menopausal women against fatal ischaemic heart disease.     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Summary Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (–27%) and phospholipids (–19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

Effects of long-term treatment with simvastatin on plasma lipids and lipoproteins in patients with primary hypercholesterolemia

Summary We investigated long-term hypolipidemic effects and clinical safety of simvastatin, a new competitive inhibitor of 3-hydroxy-methylglutaryl coenzyme A reductase in 24 patients with familial and non-familial hypercholesterolemia. Patients received up to 40 mg simvastatin for a period of 30 months. Significant decreases were noted in plasma cholesterol (30%), plasma triglycerides (25%), very low density lipoprotein-cholesterol (26%), and low density lipoprotein-cholesterol (40%), whereas an increase in plasma high density lipoprotein-cholesterol (11%) was observed. Furthermore, the percentage decrease in plasma low density lipoprotein cholesterol was independent of individual baseline concentrations. Simvastatin did not alter the composition of low density lipoproteins or high density lipoproteins. The percentage decrease in total plasma and low density lipoprotein-cholesterol was independent of apoprotein E isoforms and low density lipoprotein-receptor activity as assayed in cultured fibroblasts. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. Clinical chemistry indices and hematological, as well as endocrinological parameters remained within normal limits and ranges.Abbreviations VLDL very low density lipoprotein - LDL low density lipoprotein - HDL high density lipoprotein - CHD coronary heart disease - LDL-C low density lipoprotein-cholesterol - FH familial hypercholesterolemia - HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A - HELP heparin extracorporeal low density lipoprotein precipitation This work was supported by a grant from the Deutsche Forschungsgemeinschaft to A.K. Walli (Wa 458/I-1)Dedicated to Prof. Dr. med. F. Scheler on the occasion of his 65th birthday     

Variability in the response of different male subjects to the effect of marathon running on the increase in plasma high density lipoprotein

Summary The acute effects of running a 42.2 km marathon race on the concentration and composition of the plasma lipoproteins were studied in 56 men of varying fitness, training experience, age and physical characteristics. There was no change in the mean concentration of total serum cholesterol, but a 10.9% increase (P<0.001) in the mean concentrations of high-density lipoprotein cholesterol (HDL-TC), representing an 11.1% increase (P<0.001) in the cholesteryl ester (CE) and 9.9% increase (P<0.001) in the unesterified cholesterol (UC) moieties of HDL. The ratio of total serum cholesterol to HDL-TC decreased significantly (P<0.001) during the exercise. Changes in lipoprotein concentrations during the marathon varied considerably between individual subjects, with a small proportion of subjects exhibiting relatively large increases or decreases in HDL-TC, HDL-CE and HDL-UC. Small sub-populations of runners were identified who showed abnormally large decreases in HDL-UC and abnormally small increases in HDL-CE relative to HDL-UC. A correlation (P<0.05) was found between the average weekly mileage of training and the increase in HDL-TC, whilst faster runners (finishing time <3 h; n=13) had a significantly greater (P<0.02) increase in HDL-TC than slower runners (>4 h; n=14). The observed alterations in the lipoproteins are consistent with increased rates of lipolysis of triacylglycerol-rich lipoproteins and of cholesterol esterification during the marathon and suggest that the effect of exercise on the activities of the enzymes that catalyse these processes may vary considerably between different subjects and may be modulated by training and other factors.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins - HDL-TC high-density lipoprotein-total cholesterol - HDL-CE cholesteryl ester - HDL-UC unesterified cholesterol     

Lipoprotein pattern in long-term diabetes of an at least 35 years' duration

Summary All diabetic patients suffering from the disease for at least 20 years and living in the closed area of the Erfurt district in 1970 have been followed prospectively since that time. In 47 of them still alive in 1985, i.e. after more than 35 years of diabetes, serum lipid and apolipoprotein concentrations were measured and compared to those of non-diabetic subjects without cardiovascular diseases (n=47) pair-matched by sex, age, and body weight. In males (n=27) significantly (p<0.01) higher levels of HDL cholesterol and apolipoprotein A–I as well as lower concentrations of triglycerides and a lower total cholesterol/HDL cholesterol risk ratio than in nondiabetic control subjects could be found. In long-term diabetic females (n=20), apolipoprotein A–I levels were also increased (p<0.02). Trends in HDL cholesterol and triglycerides were similar to those found in males but did not reach statistical significance. Higher concentrations of total cholesterol (p<0.02), LDL cholesterol (P<0.05), and apolipoprotein B (p<0.02), however, did not fit in with a beneficial lipoprotein pattern. The frequency of pathological lipoprotein patterns was not higher than among the non-diabetic control subjects (32% and 40%, respectively). According to these findings an antiatherogenic lipoprotein pattern might be considered, at least in males, as one of the determinants causing the multifactorial event of long-term survival in diabetes.Abbreviations ECG electrocardiogramm - Hb haemoglobin - HDL high density lipoproteins - LDL low density lipoproteins - SD standard deviation - VLDL very low density lipoproteins     

An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia

An international panel of the International Atherosclerosis Society has developed a new set of recommendations for management of dyslipidemia. The panel identifies non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for higher risk subjects. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or regions. Secondary prevention emphasizes use of cholesterol-lowering drugs to attain optimal levels of atherogenic lipoproteins.     

Lipid profile of body builders with and without self-administration of anabolic steroids

Summary Twenty-four top-level body builders [13 anabolic steroid users (A); 11 non-users (N)] and 11 performance-matched controls (C) were examined to determine the effect on lipids, lipoproteins and apolipoproteins of many years of body building with and without simultaneous intake of anabolic steroids and testosterone. After an overnight fast, triglycerides (TG), total cholesterol (TOTC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), the HDLC subfractions HDL₂C and HDL₃C, as well as apolipoprotein A-I (Apo A-I), apolipoprotein A-II (Apo A-II) and apolipoprotein B (Apo B) were determined. Both A and N, compared to C, showed significantly lower HDLC and higher LDLC concentrations, with the differences between A and C clearly pronounced. In a subgroup of 6 body builders taking anabolic steroids at the time of the study, HDLC, HDL₂C, HDL₃C, Apo A-I and Apo A-II were all significantly lower and LDLC was significantly higher than in a second subgroup of 7 body builders who had discontinued their intake of anabolic steroids at least 4 weeks prior to the study. In some single cases HDLC was barely detectable (2–7 mg·dl⁻¹). The TG and TOTC remained unchanged. The present findings suggest that many years of body building among top-level athletes have no beneficial effect on lipoproteins and apolipoproteins. Simultaneous use of anabolic steroids results in part in extreme alterations in lipoproteins and apolipoproteins, representing an atherogenic profile. After discontinuing the use of anabolic steroids, the changes in lipid metabolism appear to be reversible.     

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00±0.15, 5.36±0.17 (P<0.01), 5.63±0.13 (P<0.05) mmol/l, respectively for total cholesterol; 4.13±0.15, 3.64±0.15 (P<0.05), 3.82±0.12 (P<0.05) mmol/l, respectively for LDL-cholesterol; 48.19±9.90, 26.59±5.53 (P<0.03), 25.12±4.62 (P<0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r=−0.27, P<0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16±0.07 mmol/l) than in the premenopausal group (0.96±0.07) or postmenopausal group not using HRT (0.87±0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.     

Lipoprotein Metabolism in Dogs and Cats

High-density lipoproteins (HDL) are the predominant lipoproteins in plasma of dogs and cats and are the major cholesterol-carrying particles. Two HDL subfractions are identifiable in dog: small, dense particles (equivalent to human HDL₃) and large, buoyant particles called HDL₁, which overlap in hydrated density with low-density lipoproteins (LDL). The HDL₁ are enriched in cholesterol and apolipoprotein (apo) E, and are prevalent in dogs fed high amounts of cholesterol and, or, saturated fat, when they are also referred to as HDL_c. Lipoproteins similar to human HDL₂ and HDL₃ are identifiable in feline plasma, along with trace HDL₁. Lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyl transferase (LCAT) activities are present in dogs and cats. Both species lack significant cholesteryl ester transfer protein activity, and reverse cholesterol transport is probably accomplished by receptor-mediated hepatic uptake of HDL₁. Methods for the measurement of canine and feline plasma lipoprotein-cholesterol concentrations, apolipoprotein concentrations, and the activities of LPL, HL and LCAT have been developed. Together with oral and intravenous fat tolerance tests, these methods provide the basis for studying lipoprotein metabolism in cats and dogs.Originally presented at ECCP 95.     

The acute effect of marathon running on plasma lipoproteins in female subjects

Summary The acute effect of running a 42.2 km marathon race on plasma lipoproteins was investigated in 12 female subjects (aged 21 to 41 years). During the race there was a significant increase (P<0.01) in the concentration of total plasma cholesterol. The mean post-race concentration of high density lipoprotein cholesterol (HDL-C) was 64.0±16.2 (SD) mg 100 ml^–1, compared with 52.1±14.0 mg 100 ml^–1 before the race, representing a significant increase (P<0.002). There was no significant difference in the concentration of very low density lipoprotein (VLDL) or low density lipoprotein (LDL) before and after the exercise. The mean concentration of the cholesteryl ester moiety of the HDL increased from 43.7±12.3 to 54.3±15.7 mg 100 ml^–1 (P<0.002), while there was no significant change in the concentration of the unesterified cholesterol, phospholipid, triacylglycerol or protein moieties of the HDL. The relative proportions of apolipoproteins A-I, A-II, C and E remained unchanged during the exercise. The changes in the concentration of each of the lipoprotein fractions observed during the marathon varied considerably between subjects. The individual increases in the concentration of HDL-C ranged from 4.1 to 28.4 mg 100 ml^–1, while both increases and decreases in individual concentrations of VLDL and LDL as well as of total plasma cholesterol were observed. These observations suggest that women undergo greater changes in HDL-C concentration than men during acute exercise, while considerable variation between individuals occurs.     

Apolipoprotein genes and atherosclerosis

Summary In order to elucidate the genetic abnormalities underlying lipoprotein disorders associated with coronary heart disease susceptibility, researchers have looked for candidate genes. The studies have focused particularly on the lipoprotein transport genes. Relatively common as well as rare mutations have already been identified in several of these genes. In addition, further metabolic and genetic studies indicate that some of these loci harbor significant, but as yet undefined, genetic variation. In the next few years, it is not unreasonable to expect that all or most of the significant mutations at these loci will be catalogued. It is too early to know whether this will be sufficient to explain the genetic basis of altered lipoprotein levels or whether new loci will need to be investigated. Additional candidate gene loci might be those coding for genes involved in intracellular cholesterol metabolism, cholesterol absorption, or insulin resistance. New loci may also be revealed by the technique of reverse genetics. A more complete understanding of the genetics of atherosclerosis susceptibility will probably also entail the identification of variants at genetic loci that control both the reaction of the blood vessel wall to atherogenic lipoproteins and the thrombosis system. Investigation of the genetic basis of coronary heart disease susceptibility remains a worthwhile and lively field, with important clinical and public health ramifications.Abbreviations LPL lipoprotein lipase - HL hepatic lipase - LCAT ecithin cholesteryl acyltransferase - CETP cholesteryl ester transfer protein - RFLP restriction fragment length polymorphism - FCR fractional catabolic rate - HDL, LDL, VLDL, SDL high, low, very low, intermediate density lipoproteins     

The effect of oestrogen implants on high density lipoproteins and its subfractions in women in their pre-mature menopause

Oestrogen is recognized as having profound effects on lipid and lipoprotein levels. It is also considered as the agent protecting the pre-menopausal woman from arteriosclerotic cardiovascular disease. High density lipoprotein (HDL) has also been ascribed a protective role against the development of arteriosclerosis. The effect of natural oestrogen (17β-oestradiol) administered in the form of a subcutaneous pellet on concentrations of lipids and lipoproteins, particularly high density lipoproteins and its subfractions were determined in three young women with premature menopause. Plasma cholesterol, low density lipoprotein and very low density lipoprotein and very low density lipoprotein levels decreased following oestrogen implantation. High density lipoproteins and in particular subfraction 2 (density cut 1.063-1.125 gm/ml) and subfraction 3 (density cut 1.125-1.21 gm/ml) increased profoundly but there was a slight fall in the HDL 2/HDL 3 cholesterol ratio. The HDL/LDL cholesterol ratio increased from 0.21 to 0.46. A decrease in the urinary FSH levels paralleled these changes in the lipoprotein concentrations. Oestrogen administered in this form, unlike other oestrogen or mixed oestrogen-progestogen compounds is a definite modifier of arteriosclerotic risk, and as such could be given therapeutically in menopausal hypercholesterolemic females.     

Effects of fish oil concentrate on lipoproteins and apolipoproteins in familial combined hyperlipidemia

Summary The effects of two moderate doses of long-chain n-3 fatty acids (3.0 and 4.5 g EPA + DHA per day for 4 weeks each) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia (FCH) were studied in a double-blind, placebo-controlled clinical trial. In nine patients with FCH n-3 fatty acids led to a statistically significant, dose-dependent fall in very low density lipoprotein (VLDL) triglycerides (3 g/day: –42%, 4.5 g/day: –55%) VLDL cholesterol (3 g/day: –41%, 4.5 g/day: –47%), and VLDL apolipoprotein (apo) B-100 (3 g/day: –40%, 4.5 g/day: –56%). No overall change in low-density lipoprotein (LDL) cholesterol was found, as confirmed statistically. However, when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently (from pretreatment 4.80±0.93 mmol/l to 5.70+0.93 mmol/l LDL cholesterol after 4.5 g/day) in four. LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly. High-density lipoprotein (HDL) cholesterol was unchanged; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19% (P<0.05) during fish oil treatment. We conclude that in FCH moderate doses of long-chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides, VLDL cholesterol, and VLDL apo B. LDL cholesterol must, however, be monitored during treatment as it may rise substantially in some although not in all patients with this disease.Abbreviations EPA eicosapentaenoic acid - DHA docosahexaenoic acid - FCH familial combined hyperlipidemia - VLDL very low density lipoprotein - LDL low-density lipoprotein - HDL high-density lipoprotein - apo apolipoprotein Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Hepatic glucose-6-phosphate dehydrogenase, cholesterogenesis, and serum lipoproteins in liver regeneration after partial hepatectomy

Liver regeneration after partial hepatectomy was used as an experimental model for studying mammalian cell division and replication. The rate of cell proliferation in this hyperplastic model was correlated with hepatic de novo synthesis of cholesterol, with the hexose monophosphate shunt pathway of glucose metabolism, and with serum lipoproteins. An increase of hepatic cholesterol esters and of incorporation of tritiated water in cholesterol esters was observed at 24 hr after partial hepatectomy. Partial hepatectomy also resulted in an increase of hepatic glucose-6-phosphate dehydrogenase and in alteration of serum lipoproteins, primarily due to a selective decline in high density lipoprotein fraction.     

Effects of ethanol on lipids and atherosclerosis.

Moderate alcohol consumption is associated with an increase in plasma high density lipoprotein (HDL) cholesterol concentration and a decrease in low density lipoprotein (LDL) cholesterol concentration. Changes in the concentration and composition of lipoproteins are estimated to account for more than half of alcohol's protective effect for coronary heart disease. Alcohol intake also affects plasma proteins involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, and phospholipases. In addition, alcohol intake may result in acetaldehyde modification of apolipoproteins. Furthermore, "abnormal" lipids, phosphatidylethanol and fatty acid ethyl esters are formed in the presence of ethanol and are associated with lipoproteins in plasma. Ethanol and ethanol-induced modifications of lipids may modulate the effects of lipoproteins on the cells in the arterial wall. The molecular mechanisms involved in these processes are complex, requiring further study to better understand the specific effects of ethanol in the pathogenesis of atherosclerosis. This review discusses the effects of ethanol on lipoproteins and lipoprotein metabolism, as well as the novel effects of lipoproteins on vascular wall cells.     

Glucose tolerance,plasma lipoproteins and tissue lipoprotein lipase activities in body builders

Summary Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118±4%), eight weight-matched (RBW 120±5%) and seven normal-weight controls (RBW 111±3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P<0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P<0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and .Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL₂ and HDL₃ cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.The results indicate that a shift in body composition from the adipose to the muscular type is associated with 1) lower glucose and insulin levels during the OGTT and 2) decrease in total and VLDL triglyceride and in total and LDL cholesterol levels but unchanged HDL cholesterol level. Thus, body builders are characterized by some metabolic features which decrease the risk of coronary heart disease. In contrast to aerobic training, body building does not influence HDL or its subfractions.     

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH autoimmune hyperlipidemia - Chol cholesterol - HDL high density lipoproteins - HLP hyperlipoproteinemia - HTGL hepatic triglyceride lipase - IDL intermediate density lipoproteins - IEF isoelectric focusing - Ig immunoglobulin - LDL low density lipoproteins - LPL lipoprotein lipase - PL phospholipids - TG triglycerides - VLDL very low density lipoproteins     

Association between sympathetic activity and the atherogenic serum cholesterol fraction

Summary A possible modulating influence of nor-adrenergic activity on serum lipoproteins was assessed under placebo conditions and following 4 weeks of sympathetic neurone blockade with debrisoquine in 9 normal subjects, 11 patients with mild essential hypertension, 9 normotensive, and 9 hypertensive hemodialysis patients. Plasma nor-epinephrine (NE) did not differ significantly among groups on placebo and was consistently reduced (P<0.05–0.001) by sympathetic blockade. The latter also decreased (P<0.05–0.001) plasma total cholesterol (C) as well as low and very low density lipoprotein cholesterol (LDL + VLDL-C) in the three patient groups. In the two dialysis groups, basal levels of plasma triglycerides (Tg) were increased and high density lipoprotein cholesterol (HDL-C) was diminished (P<0.01–0.001); sympathetic blockade lowered Tg and raised HDL-C (P<0.01–0.001). In normal subjects, sympathetic blockade did not significantly modify plasma lipoproteins. In the three patient groups, significant correlations (r=0.62–0.88;P<0.05–< 0.001) existed between (a) basal plasma NE and total C or LDL + VLDL-C and (b) debrisoquineinduced changes in NE and changes in total LDL + VLDL-C. These findings suggest that in essential hypertension as well as in hemodialysis patients, the atherogenic C fraction, represented by LDL + VLDL-C, may be modulated by the nor-adrenergic activity.Supported by the Schweizerischer Nationalfonds für wissenschaftliche Forschung     

Lipoprotein composition and serum Lp(a) lipoprotein in hypobetalipoproteinaemia.

A family with hypobetalipoproteinaemia was studied to examine the Lp(a) lipoprotein, lipoprotein cholesterol, and triglyceride composition of the serum lipids. Lp(a) lipoprotein was measured by immunoassay. Serum lipoproteins were separated by ultracentrifugation. Cholesterol and triglycerides were measured using standard enzymatic assays. Serum apolipoprotein B was low and Lp(a) undetectable in the index patient and in her father and son. Separation of the lipoproteins by ultracentrifugation showed a low cholesterol content of serum low density lipoprotein in the affected family members and also a low triglyceride content of high density lipoprotein particles in two affected members. It is concluded that serum lipoprotein cholesterol is altered in hypobetalipoproteinaemia, and family members of index cases have undetectable serum Lp(a) lipoprotein concentrations.     

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.