Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BACKGROUND. The role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. METHODS AND RESULTS. The relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, less than 5.2 mmol/l; triglycerides, less than 2.3 mmol/l), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles epsilon 2 and epsilon 4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD. CONCLUSIONS. Lipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.     

Accumulation of cholesteryl esters and triglycerides in cultured macrophages incubated with plasma very low density lipoproteins from rats fed on casein or soybean protein diets containing moderate levels of cholesterol

Even when administered at a comparatively low level, dietary cholesterol produces significant changes in the properties of plasma lipoproteins in rats, particularly the d less than or equal to 1.006 g/ml fraction (VLDL). The occurrence of these changes is promoted by dietary casein. To test the hypothesis that these dietary-induced perturbations might include properties influencing lipoprotein-cell interactions of relevance to atherogenesis, cultured mouse peritoneal macrophages were incubated with VLDL isolated from male rats fed on diets containing either 0, 0.25 or 0.5% cholesterol with casein or soybean protein, respectively, as the sole source of protein. No increase in cholesteryl ester content, and a comparatively small rise in triglyceride content, was observed in macrophages incubated with VLDL from rats fed on cholesterol-free diets. In contrast, a significant and apparently saturable cellular accumulation of cholesteryl esters as well as triglycerides was produced by VLDL from cholesterol-fed rats. The curves showing cellular lipid accumulation versus VLDL-protein (or VLDL-cholesterol) content in the cell medium indicated different cellular affinity for VLDL from casein-fed rats in comparison with VLDL from soybean protein-fed rats. The apoprotein composition of VLDL differed between groups of rats fed on different types of dietary protein with higher proportions of apo C's in the casein-fed rats. In addition, cholesterol feeding resulted in increased proportions of apo A-I and apo A-IV in the plasma VLDL fraction.     

Effects of castration and testosterone administration on serum lipoproteins and their apoproteins in male spontaneously hypertensive rat

Serum triglyceride and very low density lipoprotein (VLDL) concentrations were higher in male spontaneously hypertensive rat than in male control Wistar Kyoto rat, whereas serum cholesterol, phospholipids, and high density lipoprotein (HDL) concentrations were lower. Castration of hypertensive rats induced an increase in serum cholesterol, phospholipids, and HDL, and a decrease in serum triglyceride and VLDL. The cholesterol content of HDL increased, whereas the triglycerides decreased after gonadectomy of hypertensive rats. These changes in serum lipids and lipoproteins could be reversed by the administration of testosterone. Apolipoprotein E contents in VLDL and HDL of hypertensive rats were low when compared with control rats but rose after castration and could be reduced by testosterone administration. Hypertensive rats accumulated triglycerides and cholesterol in the liver, which resulted in an increase of liver weight. Castration reduced the hepatic lipids as well as liver weight. The effects of castration and testosterone treatment on lipids and lipoproteins were more prominent in spontaneously hypertensive rats than in control rats. These results suggest that testosterone reduces VLDL catabolism which is related to changes of apolipoprotein composition, and that hypertensive rats are more sensitive to testosterone than control rats.     

Metabolic effects of a biphasic oral contraceptive preparation containing ethinyloestradiol and desogestrel on serum lipoproteins and apolipoproteins

The effect of the administration of a biphasic oral contraceptive containing ethinyloestradiol and desogestrel on the distribution and composition of serum lipoproteins was studied in a group of 17 healthy female volunteers. The women were treated for a period of 6 months and compared with a control group of ten untreated volunteers. The serum lipoproteins were fractionated by density gradient ultracentrifugation into very low density lipoproteins (VLDL), low density lipoproteins (LDL), and into the high density lipoprotein (HDL) subfractions 2 and 3 (HDL2, HDL3). Lipids and apolipoproteins were assayed in the various fractions. No modification of either the lipid or apolipoprotein concentrations was observed in the control group. In the treated group, sex hormone-binding globulin (SHBG) and cortisol-binding globulin (CBG), and the serum content of cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) increased significantly after 3 and 6 months. The cholesterol and apolipoprotein B (apo B) content of VLDL increased significantly after 3 and 6 months, but remained unchanged in LDL. High density lipoprotein subfraction 2 (HDL2)-cholesterol was significantly increased after 3 and 6 months but apo A-I only after 6 months. Since apo A-II did not change, the apo A-I/A-II ratio increased significantly after 6 months of treatment. In the HDL3 fraction, the apo A-I increase was significant after 3 and 6 months, while the increase of apo A-II was significant after 6 months. The apo A-I/A-II ratio remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma vitamin E, apolipoprotein B and HDL-cholesterol in middle-aged men from southern Italy

Plasma vitamin E, HDL-cholesterol, apolipoprotein B and triglycerides were measured in an apparently healthy, male, random population sample (n = 74) from Southern Italy. Plasma vitamin E concentration was positively correlated to that of serum cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B (all P less than 0.001). The results of partial correlation analysis showed that apo B, the apolipoprotein constituent of LDL, was related to vitamin E independently of serum triglycerides, a fairly accurate marker of VLDL. On the other hand, triglycerides were related to vitamin E independently of apo B. Both correlations were much weaker if an adjustment was performed for non-HDL-cholesterol. No independent relationship was demonstrated between plasma vitamin E and HDL-cholesterol.     

Mechanism of action of niacin on lipoprotein metabolism

It is generally accepted that the increased concentrations of apolipoprotein (apo) B containing very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL), and decreased levels of apo AI containing high-density lipoproteins (HDL) are correlated to atherosclerotic cardiovascular disease. Current evidence indicates that the post-translational apo-B degradative processes regulate the hepatic assembly and secretion of VLDL and the subsequent generation of LDL particles. The availability of triglycerides (TG) for the addition to apo B during intracellular processing appears to play a central role in targeting apo B for either intracellular degradation or assembly and secretion as VLDL particles. Based on the availability of TG, the liver secretes either dense TG-poor VLDL2 or large TG-rich VLDL1 particles, and these particles serve as precursors for the formation of more buoyant or small, dense LDL particles by lipid transfer protein- and hepatic lipase-mediated processes. HDLs are a heterogenous class of lipoproteins, and apo AI (the major protein of HDL) participates in reverse cholesterol transport, a process by which excess cholesterol is eliminated. Recent studies indicate that HDL particles containing only apo A-I (LPA-I) are more effective in reverse cholesterol transport and more anti-atherogenic than HDL particles containing both apo A-I and apo A-II (LPA-I+A-II).     

Levels of serum lipids, apolipoproteins A-I and B and pseudocholinesterase activity and their discriminative values in patients with coronary by-pass operation

Serum lipids and apoproteins A-I and B were measured in 115 male patients and serum pseudocholinesterase activity (PChE) was determined in 83 patients with 3 vessel coronary artery disease (CAD). The control subjects were matched according to sex, smoking, relative weight and age and were free from heart disease. The CAD patients had significantly higher serum VLDL cholesterol and triglyceride levels and lower HDL cholesterol and apo A-I levels and lower HDL to total cholesterol ratio than the controls. The concentrations of serum total cholesterol and LDL cholesterol were only slightly (6.4% and 8.8%, on an average) higher in CAD patients than in controls. The apo B levels of CAD patients were also slightly lower in patients than in controls. The CAD patients had slightly higher PChE activities than controls. The ratios of apo A-I to PChE and HDL cholesterol to PChE were significantly (about 30%, P less than 0.001) lower in patients than in controls. In discriminant analysis between the groups HDL cholesterol and apo A-I showed the best (74% success in reclassifying the patients to correct groups), and total cholesterol, triglycerides, LDL cholesterol and apo B remarkably weak discriminating power among the single variables of serum lipids and lipoproteins. In discriminating analysis the apo A-I/PChE and HDL cholesterol/PChE ratios showed relatively high (77.1 and 71.1% success from the patients to correct groups) and serum PChE activity weak discriminating power. These results indicate that low levels of HDL cholesterol and apo A-I and the low ratio of HDL cholesterol to total cholesterol are the most potent metabolic risk factors for 3 vessel coronary artery disease in a population with relatively high serum total cholesterol level. The determinations of apo A-I/PChE and HDL cholesterol/PChE ratios may be an additional, valuable tool in discriminating the risk for CAD.     

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

Aims/hypothesis Very low density lipoprotein (VLDL) particles are heterogeneous, comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim of the study was to examine the distribution and composition of VLDL subspecies in type 2 diabetes.Subjects, materials and methods We studied the composition and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic patients and 93 control subjects between 50 and 75 years of age. Lipoprotein subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by nephelometry and apo CII in serum by a commercial kit using a single radial immunodiffusion method.Results The concentrations of VLDL 1, VLDL 2 and intermediate density lipoprotein were significantly increased in type 2 diabetes subjects, the change being most marked for VLDL 1. There was a strong linear correlation between VLDL 1 triglycerides and plasma triglycerides in both groups (r=0.879, p<0.001 and r=0.899, p<0.001). Diabetic subjects had markedly higher plasma ratios of apo CII:apo CIII and apo CIII:apo E. Despite elevated plasma apo CIII, type 2 diabetic subjects had a relative deficiency of apo CIII in all TRL subspecies, suggesting profound disturbances of apo CIII metabolism.Conclusions/interpretation The elevation of VLDL 1 triglycerides is the major determinant of plasma triglyceride concentration in normal subjects and in type 2 diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2 diabetes.     

Apolipoprotein C subtype distribution in type 2 diabetes mellitus

Plasma lipid levels and apolipoprotein C (apo C) composition of VLDL were investigated in a group of Type 2 diabetic patients at first attendance at the outpatient clinic and before any therapeutic intervention. Patients were distributed into two groups of 26 individuals, normo- and hyperlipidaemic, respectively, and compared with two matched control groups. Normolipidaemic diabetic patients had higher serum triglycerides, VLDL cholesterol, and lower HDL cholesterol than matched normolipidaemic control subjects. While hyperlipidaemic non-diabetic individuals showed increased apo C II and decreased apo C III-1 percentages when compared with normolipidaemic non-diabetic individuals (12.1 +/- 4.9 vs 8.5 +/- 3.2% and 44.0 +/- 6.7 vs 48.1 +/- 7.0%, respectively, mean +/- SD, both with p less than 0.05), the relative distribution of apo C III isoforms and apo C II was similar in both normo- and hyperlipidaemic diabetic patients.     

Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy

Abstract. To study the possible importance of variation at the apolipoprotein (apo) E gene locus for the clinical expression of heterozygous familial hypercholesterolaemia (FH), we determined apo E phenotype and serum lipoprotein pattern in 120 patients with FH. The allele frequency of the patients studies were: ε2 0.033, ε3 0.733, and ε4 0.233. There was no influence of apo E phenotype on the serum concentrations of total, VLDL, LDL or HDL cholesterol, triglycerides, or of apo AI, B or (a). Serum concentrations of apo E were significantly higher in patients with the apo E 3/3 phenotype compared to those with apo E 4/3 or 4/4, and the highest concentrations were found in patients carrying the ε2-allele. The cholesterol-lowering response to therapy with cholestyramine or pravastatin was not related to apo E phenotype. It is concluded that variation at the apo E gene locus is not of major importance for the expression of heterozygous FH.     

Quantitative and qualitative serum lipoprotein analysis. Part 1. Studies in healthy men and women.

Preparative ultracentrifugal and electrophoretic analysis of serum lipoproteins was performed in 30-70-year-old healthy, fasting males (N = 80) and females (N = 77), randomly selected from the Uppsala region, Sweden. The concentrations of cholesterol and triglycerides in total serum and in VLDL,LDL and HDL lipoprotein classes are reported. Total serum, VLDL and LDL triglycerides and cholesterol concentrations increased with age, while HDL cholesterol and triglyceride concentrations did not vary with age. Overweight persons had higher total serum triglyceride, higher VLDL cholesterol and triglyceride and lower HDL cholesterol levels. The upper 90% population limit values for non-overweight males/females were: total triglycerides (mmol/l) 2.5/2.0, total cholesterol (mg/100 ml) 298/300, VLDL triglyceride 1.80/1.05, VLDL-cholesterol 32/33, LDL triglyceride 0.69/0.69, LDL cholesterol 210/218, HDL triglyceride 0.32/0.34 and HDL-cholesterol 69/93. The 2 major differences between males and females were that females had lower VLDL but higher HDL concentrations. For VLDL there was a very strong and for LDL a moderately strong positive correlation between cholesterol and triglyceride contents. In HDL however, the mearsured amounts of cholesterol and triglycerides did not correlate at all. Sinking pre-beta lipoproteins was found in about 25% of cases and a second pre-beta band floating at d 1.006, late pre-beta, was found in 35% of male and 25% of female subjects. Subjects with sinking pre-beta lipoprotein did not differ from other subjects with regard to the concentration of cholesterol and triglycerides in the 3 lipoprotein classes. Males, but not females, with the late pre-beta (LPB), had an increased amount of cholesterol in VLDL and a raised cholesterol-triglyceride ratio in this lipoprotein class. Also the LDL triglyceride level was increased in males with the late pre-beta lipoprotein.     

Lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations were measured at 10 days and 4 months after myocardial infarction (MI) in 60 young Kuwaiti male MI survivors below the age of 40 years. Controls were matched for age, relative weights, smoking, dietary habits and physical activities. The young MI survivors had significantly higher levels of total and LDL-cholesterol, and ratios of LDL/HDL- and LDL/HDL2-cholesterol. Total VLDL and LDL triglycerides, and phospholipids were also elevated in MI survivors compared to controls. Similarly, plasma and LDL-apo B as well as the ratios of apo B/apo A-I were higher in the MI group. There was no significant change in the levels of VLDL and HDL3-cholesterol and of apo A-II in these patients compared to their controls. Concentrations of HDL- and HDL2-cholesterol and of plasma and HDL apo A-I were significantly lower in the young MI survivors compared to the control subjects. The better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2-cholesterol greater than apo B greater than apo A-I greater than VLDL-triglyceride greater than HDL-cholesterol greater than LDL/HDL2-cholesterol greater than triglycerides. The data indicate that measurement of HDL2-cholesterol, apo B and apo A-I may be useful indicators in assessing coronary artery disease risk than triglycerides (TG), total cholesterol (TC), LDL-cholesterol and HDL-cholesterol.     

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.     

Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins

The effects of the plasma pattern of GH on serum and lipoprotein levels of total cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B 48/100 (apo B), and apolipoprotein E (apo E) were studied in hypophysectomized female Sprague-Dawley rats, which had been given replacement therapy with L-T4 and hydrocortisone. Bovine GH (1 mg/kg.day) was administered sc either continuously by means of osmotic minipumps or by two daily injections. Serum lipoproteins were separated by sequential ultracentrifugation into very low density lipoproteins [density (d) less than 1.006 g/ml], low density lipoproteins (LDL; d 1.006-1.063 g/ml) and high density lipoproteins (HDL; d 1.063-1.21 g/ml). The content of total cholesterol and triglycerides were then determined. Apo A-I, apo B, and apo E were isolated from rat serum and antibodies raised in rabbits. In serum and in lipoprotein fractions, the content of apo A-I, apo-B, and apo E were determined by electroimmunoassay. After hypophysectomy, there occurred a decrease in serum cholesterol and serum levels of apo A-I and apo E, in spite of replacement therapy with T4 and cortisone. Similar changes were also observed in HDL. In contrast, apo B, cholesterol, and triglycerides were increased in LDL. Estradiol treatment had no effect on these changes. Continuous infusion of GH resulted in an increase in cholesterol and apo E in serum and HDL to the levels of intact females. In contrast, GH given twice daily had no effect. Therefore, the sexually dimorphic secretion of GH may be important for the regulation of sex differences in apo E and HDL cholesterol levels. There were no consistent effects of GH treatment on the levels of apo A-I in serum or HDL, but GH treatment resulted in a decrease in apo B and triglycerides in both serum and LDL, regardless of the mode of administration. This suggests that GH regulates the serum and LDL levels of apo B and triglycerides independently of the secretory pattern.     

Effects of atorvastatin on postprandial plasma lipoproteins in postinfarction patients with combined hyperlipidaemia

Enhanced and prolonged postprandial lipaemia is implicated in coronary and carotid artery disease. This study assessed the effects of atorvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on postprandial plasma concentrations of triglyceride-rich lipoproteins (TRLs). Sixteen middle-aged men with combined hyperlipidaemia (baseline low density lipoprotein (LDL) cholesterol and plasma triglyceride concentrations (median (interquartile range) of 4.54 (4.17-5.26)) and 2.66 (2.04-3.20) mmol/l, respectively) and previous myocardial infarction were randomised to atorvastatin 40 mg or placebo once daily for 8 weeks in a double-blind, cross-over design. The apolipoprotein (apo) B-48 and B-100 contents were determined in subfractions of TRLs as a measure of chylomicron remnant and very low density lipoprotein (VLDL) particle concentrations (expressed as mg apo B-48 or apo B-100 per litre of plasma), in the fasting state and after intake of a mixed meal. Atorvastatin treatment reduced significantly the fasting plasma concentrations of VLDL cholesterol, LDL cholesterol and VLDL triglycerides (median% change) by 29, 44 and 27%, respectively, and increased high density lipoprotein (HDL) cholesterol by 19%, compared with baseline. The postprandial plasma concentrations of large (Svedberg flotation rate (Sf) 60-400) and small (Sf 20-60) VLDLs and chylomicron remnants were almost halved compared with baseline (mean 0-6 h plasma concentrations were reduced by 48% for Sf 60-400 apo B-100, by 46% for Sf 60-400 apo B-48, by 46% for Sf 20-60 apo B-100 and by 27% for Sf 20-60 apo B-48), and the postprandial triglyceridaemia was reduced by 23% during active treatment. In conclusion, atorvastatin 40 mg once daily causes profound reductions of postprandial plasma concentrations of all TRLs in combined hyperlipidaemic patients with premature coronary artery disease.     

Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.     

Adenoviral delivery of low-density lipoprotein receptors to hyperlipidemic rabbits: Receptor expression modulates high-density lipoproteins

Plasma concentrations of low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs) are inversely related in several dyslipoproteinemias. To elucidate the interactions between these lipoproteins, we used a recombinant adenovirus (hLDLR-rAdV) to express human LDL receptors (hLDLRs) in LDL receptor-deficient rabbits. hLDLR-rAdV administration resulted in hepatocyte expression and a reduction of total, intermediate-density lipoprotein (IDL), and LDL cholesterol. In addition, we found that hLDLR-rAdV treatment induced (1) increased very-low-density lipoprotein (VLDL) cholesterol, (2) increased VLDL, IDL and LDL triglycerides, (3) decreased α- and pre-β-migrating apolipoprotein E (apo E) and decreased pre-β-migrating apo A-I at 2 to 4 days posttreatment, and (4) increased total plasma apo A-I and pre-β-migrating apo A-I beginning 8 to 10 days posttreatment. Virtually all plasma apo A-I was present on α- and pre-β-HDL. Pre-β-HDL particles with size and electrophoretic properties consistent with nascent HDL demonstrated the greatest relative apo A-I enrichment following hLDLR-rAdV treatment. In summary, enhanced expression of hepatocyte LDLRs by hLDLR-rAdV treatment markedly altered apo A-I-containing lipoproteins and IDL and LDL. The use of recombinant viruses to express physiologically relevant genes in intact animals, analogous to transfection of cells in culture, provides a new strategy for the evaluation of effects of specific gene products on metabolic systems in vivo.     

Anomalies in composition of uremic lipoproteins isolated by gradient ultracentrifugation: relative enrichment of HDL in apolipoprotein C-III at the expense of apolipoprotein A-I

Using a discriminating gradient separation technique combined with careful analysis of lipid and apolipoprotein (apo) composition, serum lipoproteins of 20 chronically uremic patients have been compared with those of 19 normal controls matched for age and sex. In uremic subjects, serum VLDL concentration was markedly increased. These particles were enriched in protein and cholesterol and relatively poor in triglycerides (TG). They contained more frequently apo B-48, and a decreased proportion of apo E. Expressed in percent, total apo C was normal but the ratio of apo C-III2/apo C-III1 was elevated. Uremic IDL, whose serum concentration was markedly increased, were characterized by an increased proportion of protein. Total uremic LDL whose serum concentration was normal, contained less esterified cholesterol (EC) and more TG than normal LDL, their EC/TG ratio being very low. Moreover, the concentration of the mature subfraction of LDL having a mean density of 1.043 g/ml, was markedly decreased in uremic subjects. Taken together, these anomalies indicate a delayed transformation of VLDL into LDL in chronic renal failure. The decreased concentration of total HDL in uremic subjects was more marked in HDL2 (-46%) than HDL3 (-24%). Both uremic HDL2 and HDL3 were relatively enriched in TG, and uremic HDL3 were poorer in EC than normal HDL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary effects on very low-density lipoproteins in type 2 (non-insulin-dependent) diabetes mellitus

Summary To evaluate possible influences of dietary intervention on the composition of very low-density lipoproteins (VLDL), ten subjects with Type 2 (non-insulin dependent) diabetes mellitus received a hypocaloric regimen. Fifteen healthy subjects served as controls. Ultracentrifuged VLDL were analysed as cholesterol, triglycerides, apolipoprotein B (apo B), and the soluble apolipoproteins C and E (polyacrylamide gel electrophoresis in urea and densitometry) before the study, after 2 weeks and then after 3 months. Compared with the control subjects, the content of cholesterol and apo E in the VLDL was elevated in the diabetic subjects, while the area ratio of apo C-II to apo C-III₁ was lowered. After diet the reduction in VLDL was accompanied by compositional changes: a decrease of the cholesterol/triglyceride ratio and of the apo E/apo C area ratio. The apo C-II/apo C-III₁ area ratio remained unaffected. We conclude that one beneficial effect of therapeutic intervention in diabetes may lie in lowering the level of possibly atherogenic VLDL-components.     

Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction

The serum high density lipoprotein (HDL) subfractions, HDL2, and HDL3, and serum apolipoprotein AI and B (apo AI and B) were evaluated as potential indicators of the risk of ischaemic heart disease in men aged less than 60 years who had previously had a myocardial infarction and in controls with a similar socioeconomic background who had no history of myocardial ischaemia. Discriminant analysis confirmed that the combination of serum cholesterol, triglycerides, and total HDL cholesterol distinguished poorly between patients and controls. The best single discriminating variable was apo B. Stepwise discriminant analysis showed that this discrimination could be improved to a small extent by combining apo B with apo AI and parental history, but nothing was gained by measurement of serum cholesterol triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, HDL cholesterol, HDL2 or HDL3 cholesterol. Significantly more patients than controls with type IV hyperlipoproteinaemia had raised concentrations of serum apolipoprotein B, but the frequency of raised apolipoprotein B concentrations was no greater in patients with type IV hyperlipoproteinaemia than in those with normal serum lipids. The value of apo B as an indicator of cardiovascular risk should be assessed in prospective studies.