Hyperlipoproteinemic Patients Research Articles

Doppler ultrasound diagnosis of atherosclerotic lesions within lower extremity arteries in hyperlipoproteinemic patients

The purpose of this study was to establish the correlation between the intensity of atherosclerosis of the lower extremities found during Doppler examination, and the type of hyperlipoproteinaemia. An attempt was undertaken to analyze the relation of risk factors of obliterative atherosclerosis to the condition of the arteries in the lower extremities. Fifty-three men, aged 37–63 years (mean age 51 years) were examined. Hyperlipoproteinemia types IIa, IIb and IV were found in 16, 19 and 18 patients, respectively. The control group consisted of 30 healthy non-smoking men. The examination was performed using the ACUSON 128 with linear 5 and 7 MHz transducers. Doppler spectra were obtained from the external iliac, common femoral, superficial femoral, deep femoral and popliteal arteries. Simultaneously, a two-dimensional colour picture of the vessels and Doppler spectra were recorded. Blood velocity spectra were quantitatively assessed according to the classification suggested by Jager et al. The results of Doppler examination confirmed the unfavourable influence of so-called risk factors on the prevalence of atherosclerosis, especially low serum concentration of high density lipoproteins cholesterol and smoking. In addition, the examination has shown the ability to diagnose even asymptomatic atherosclerotic lesions of the arteries of the lower extremities.

Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% ( P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% ( P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL 1(1.019 < d < 1.045)-TC and LDL 1-TG in the study population as a whole but significantly increased the plasma level of LDL 1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL 2 (1.045 < d < 1.063)-TC, LDL 2-TG by 48% and 44% ( P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL 2-TC but reduced the HDL 2-TG concentration significantly ( P < 0.001). Bezafibrate increased the plasma level of HDL 3-TC by 37% and reduced the HDL 3-TG level significantly by 20% ( P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL 3a and a decrease in HDL 2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% ( P < 0.001) and 17% ( P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL 3 (HDL 3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.

Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type l

Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2)-1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high-density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease.

HDL粒子サイズと血清脂質, アポ蛋白値との関係

An attempt was made to estimate the distribution of plasma HDL subclasses according to the levels of plasma lipids and apoproteins. Twenty-five normolipidemic patients, 25 hyperlipoproteinemic patients without CHD, and 28 CHD patients participated in this study. The distribution of plasma HDL subfractions was estimated by 4-30% gradient polyacrylamide gel electrophoresis (PAGE) of plasma fraction with a density of 1.21. The absolute amounts of HDL subfractions were obtained by multiplying HDL-C amounts by the percentage of HDL PAGE subclasses. Plasma concentrations of HDL2b-C, HDL2a-C, HDL3a-C, HDL3b-C and HDL3c-C were 7.8±6.8mg/dl, 10.6±6.5mg/dl, 46.3±6.3mg/dl, 5.1±2.4mg/dl and 0.2±0.4mg/dl (mean±SD), respectively. Plasma HDL2b-C amounts were positively correlated with HDL-C (r=0.721, p<0.001) and apo A-I (r=0.545, p<0.001) levels, but were not correlated with apo A-II. Plasma HDL2a-C levels were positively correlated with HDL-C (r=0.638, p<0.001) concentrations, but were not correlated with apo A-II. The correlation coefficients with HDL-C and apo A-I were higher in HDL2b-C levels than in HDL2a-C levels. Plasma HDL3a-C amounts were positively correlated with HDL-C (r=0.365, p<o.01), apo A-I (r=0.320, p<0.02) and apo A-II (r=0.470, p<0.001) levels. Plasma HDL3b-C levels were positively correlated with apo A-I (r=0.287, p<0.02), apo A-II (r=0.530, p<0.001), apo C-II (r=0.420, p<0.001), apo C-III (r=0.344, p<0.01), and apo E (r=0.321, p<0.01) concentrations. Plasma HDL3b-C levels were not correlated with HDL-C amounts. These results indicate the following. The concomitant changes of plasma HDL-C and apo A-I levels without apo A-II alteration suggest the alteration of HDL2a and HDL2b amounts, especially HDL2b. Changes in HDL-C, apo A-I and apo A-II levels in the same direction reflect the alteration of HDL3a amounts. HDL3b might be heterogeneous because the plasma HDL3b-C level was positively correlated with many kinds of apoprotein amounts. It was therefore concluded that the changes in HDL subfractions could be estimated by the measurement of plasma HDL-C and apoproteins.

New method for isolating and quantifying intermediate and beta-very-low-density lipoprotein cholesterol

We describe a new method, useful to clinical laboratories, for assessing intermediate density (IDL) or beta-very-low-density (beta-VLDL) lipoprotein cholesterol. The technique involves selective precipitation properties of the qualitative Wieland and Seidel post-electrophoretic method that immobilizes IDL and beta-VLDL in the beta-zone of an agarose slide (Clin Chem 1973;19:1139-41). In our method, we separate low-density lipoprotein (LDL) in a second electrophoretic step, in which LDL moves toward the anode, and then quantify the cholesterol of the above lipoproteins remaining in the precipitate band at the beta-zone. Replicate within-run precision (CV) of 15 aliquots of a sera pool was 10.1%. The correlation with sequential ultracentrifugation of 30 samples was r = 0.96 (P less than 0.001). Serum reference values for 30 normal individuals are 57 +/- 7.0 mg/L. Seven phenotype III hyperlipoproteinemic patients had the highest concentrations of IDL or beta-VLDL cholesterol in serum, 1620 +/- 346 mg/L.

Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families.

Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL-deficient or partially deficient individuals.

Efficacy of cholestyramine does not vary when taken before or during meals

Compliance to cholestyramine treatment, often unsatisfactory, may become further problematic because of the common indication that the resin should not be taken with meals. Since there is no convincing data on the validity of this therapeutic schedule, 10 type IIA hyperlipoproteinemic patients received cholestyramine either before or during the 3 major meals, according to a cross-over protocol. Plasma lipid levels were monitored after 4 and 6 weeks of each treatment schedule. The efficacy of the resin, in terms of total cholesterol (−16.5% together with food vs. −17.2% before food) and of low density lipoprotein cholesterol reduction (−22.8% with food vs. −23.1% before food) did not differ. The side effect profile was also not different between the two treatment protocols. These findings suggest that there are no significant interactions between food and the anion exchange resin and that the hypocholesterolemic effect does not depend upon a specific timing, supposedly close to the gallbladder contraction. They are particularly significant in view of the future availability of new resins in liquid form, suitable for intake during meals.

Apolipoprotein E Phenotype Frequency in Type II Diabetic Patients with Different Forms of Hyperlipoproteinemia

Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia.

Lipids and testicular function.

We studied 19 male patients with primary hyperlipoproteinaemia, a control group of 28 healthy men and 44 infertile males before any treatment was undertaken. Spermiogram, seminal biochemical studies, measurements of plasma hormone levels and lipid determinations were carried out. Most hyperlipoproteinaemic patients showed abnormalities in the spermiograms and the mean values were lower than in the controls except for semen volume. Seminal biochemical determinations were normal in the majority and the hormone profile showed some abnormal values, mainly for E2. Lipid abnormalities were more common in azoospermic infertile men and mean lipid levels were higher. Correlation studies suggest that high levels of C and/or Tg are associated with poor semen quality and higher FSH levels. The results of our studies suggest that high lipid levels exert adverse direct effects at the testicular level.

Serum apolipoprotein profile of hypertriglyceridemic patients with chronic renal failure on hemodialysis: A comparison with type IV hyperlipoproteinemic patients

Thirty-three patients with chronic renal failure (CRF) and uremic hypertriglyceridemia (HTG) on hemodialysis were compared with 33 type IV hyperlipoproteinemic patients matched for age, body mass index (BMI), and triglyceride (TG) levels. The two forms of hypertriglyceridemia showed different apolipoprotein profiles: apo AI, AII, and B levels and apo CII:CIII and TG:apo CIII ratios of CRF-HTG patients were lower and apo CIII levels were higher than the levels of type IV subjects.

A young type III hyperlipoproteinemic patient associated with apolipoprotein E deficiency

A 13-year-old female patient had noticed tuberoeruptive xanthomas since 3 years of age. Her serum, VLDL, and IDL cholesterol levels were high (348, 158, and 60 mg/dL, respectively), while LDL and HDL cholesterol levels were 56 and 62 mg/dL, respectively. VLDL-cholesterol/serum triglyceride ratio was extremely high (0.86), suggesting type III hyperlipoproteinemia (HLP). Her apo E was undetectable by the single radial immunodiffusion studies and SDS-polyacrylamide gel electrophoresis. Her parents showed hypertriglyceridemia and her two siblings were normolipidemic, and their apo E levels were normal. Genomic DNA digested with BamHI or EcoRI did not show gross differences in the restriction fragment length between the apo-E-deficient patient and normal controls. Thus, apo E deficiency may be characterized by early appearance of clinical manifestations of type III HLP and higher VLDL-cholesterol/serum triglyceride ratio.

Decrease in LDL and increase in HDL concentrations in type II hyperlipoproteinaemic patients on low-dose combination therapy of cholestyramine and Complamin®

A low-dose combination of Complamin® retard (1 g t.i.d.) and cholestyramine (4 g b.i.d.) was compared with each agent alone in 2 serial open trials without dietary restriction using type IIa and IIb hyperlipoproteinaemic patients. Complamin alone produced decreases in LDL and VLDL cholesterol concentrations (up to 20%) whereas cholestyramine alone produced only a modest reduction in LDL (up to 15%). The combination produced marked, progressive reductions in total cholesterol (up to 35%) and LDL (up to 40%); reductions in VLDL (up to 45%), total triglyceride (up to 60%) and free fatty acids (up to 60%) were found only type IIb patients. The average increase in HDL-cholesterol from the 2 studies for combination therapy was 35%. No side-effects were reported or measured and compliance was excellent. The results demonstrate the potential of a method of achieving beneficial actions on lipoprotein levels with a well-tolerated therapy.

Analysis of human apolipoproteins C by isoelectric focusing in immobilized pH gradients.

Apolipoproteins C are involved in many ways in the metabolism of plasma lipoproteins. Apolipoproteins C from the delipidated VLDL of 35 controls and 165 normo- and hyperlipoproteinemic patients were analyzed by isoelectric focusing on an immobilized pH gradient, pH 4.0-5.0, with 7 M urea, which raised the apparent pH range to 4.8-5.7. This method is an improvement over conventional isoelectric focusing with carrier ampholytes with regard to both resolution and reproducibility. Due to the high resolution (0.1 pH units per cm) additional apolipoprotein C-III bands: C-III0 A1, C-III0 A2, C-III1 C and C-III2 C (the designations A, anodic, and C, cathodic, refer to direction of migration on IEF in relation to the main band) are described for the first time. The possible artifactual nature of these protein bands could be excluded. Cleavage with neuraminidase and peptidases, immunological detection and/or two-dimensional electrophoresis were used to obtain more information. The additional bands seem, in part, to be hydrolysis products of carboxypeptidase A (C-III1 C, C-III2 C). The appearance of C-III1 C and C-III2C was dependent upon the serum triglyceride concentration. The percent distribution of C apolipoproteins in very low density lipoproteins (VLDL) from control serum agreed with previously published data. Apolipoproteins C can also be focused in immobilized pH gradients from VLDL and serum without delipidation.

Serum apolipoprotein profile of patients with chronic renal failure

Serum concentrations of apolipoproteins A-I, A-II, B, C-I, C-II, C-III and E were determined by electroimmunoassay in 56 patients with chronic renal failure (CRF) in the predialytic phase. The results were compared with those obtained in asymptomatic normolipidemic subjects, patients with type IV hyperlipoproteinemia, and patients with type II diabetes mellitus. CRF patients had reduced concentrations of ApoA-I and ApoA-II, normal levels of ApoB and ApoC-I, and increased concentrations of ApoC-II and, in particular, of ApoC-III. There was a significant reduction in the levels of ApoE, especially in male patients. In comparison with type IV, hyperlipoproteinemic patients, CRF patients had lower concentrations of ApoA-I, ApoA-II, ApoB, ApoC-I and, particularly, ApoE; there was no difference in ApoC-III levels reflecting the hypertriglyceridemia common to both disorders. Similar but less marked differences were also found in comparison with type II diabetics. The findings suggest that in CRF, the accumulation of ApoC-III-enriched lipoprotein particles accompanied by a moderate hypertriglyceridemia may be caused more probably by an impaired catabolism than overproduction of triglyceride-rich lipoproteins. CRF patients with vascular disease tended to have higher serum concentrations of triglycerides, cholesterol and ApoB and lower ApoA-I/ApoC-III and ApoA-I/ApoB ratios than patients without vascular disease.

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

The primary structure of apolipoprotein E (apo E) was investigated in seven type III hyperlipoproteinemic patients with the apo E-2/2 phenotype. Six of the patients had identical two-dimensional tryptic peptide maps. These differed from the normal apo E3 map by the altered mobility of a single peptide. Amino acid analysis and sequencing showed that apo E2 in these patients had a substitution of 158 Arg----Cys. The presence of this mutation in six of the seven type III patients confirms that this is the most common form of apo E2. The seventh type III patient had a unique map with a new peptide resulting from a substitution of 136 Arg----Ser. He was heterozygous for this and for the more common apo E2 (158 Arg----Cys) variant. His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg----Ser) than apo E2 (158 Arg----Cys), as determined by cysteamine treatment and peptide mapping. This new apo E2 mutant thus appears to contribute significantly to the patient's hyperlipidemia.

Bezafibrate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hyperlipidaemia.

Bezafibrate is a lipid-lowering drug, chemically related to clofibrate. At its recommended dosage of 200 mg 3 times daily, or alternatively 400 mg once daily as a sustained-release preparation, it produces substantial reductions in plasma triglyceride and cholesterol concentrations in patients with hypertriglyceridaemia and hypercholesterolaemia, respectively. Preliminary investigations indicate that a single daily dose of 400 mg in a sustained-release preparation is as effective as 200 mg 3 times daily. In patients with any type of hyperlipoproteinaemia bezafibrate also increases the plasma HDL-cholesterol concentration. These effects are equivalent in patients with primary hyperlipoproteinaemia or hyperlipoproteinaemia secondary to diabetes or renal disease, although dosage adjustment is important in the latter group. During long term therapy (2 to 4 years) the influence of bezafibrate on the lipid profile is sustained. The lipid-lowering effects of bezafibrate are at least equivalent to those of clofibrate, fenofibrate, colestipol, probucol or sustained release etofibrate. In addition, the increase in HDL-cholesterol tends to be at least as great as with all alternative treatments studied. Bezafibrate is rapidly eliminated, and thus does not accumulate during prolonged administration in patients with normal renal function. Experimental studies have shown bezafibrate to have a complex range of effects on lipoproteins and on the enzymes and receptors involved in lipid metabolism. However, its exact mechanism of lipid-lowering action is unclear. Bezafibrate enhances anticoagulation in hyperlipoproteinaemic patients requiring anticoagulant therapy, and preliminary investigations indicate that it reduces the plasma fibrinogen concentration, especially in patients with hyperfibrinogenaemia. These properties of bezafibrate could contribute to an antiatherogenic effect of the drug, but further investigation is required to establish the drug's potential as chronic therapy in patients with hyperfibrinogenaemic atherosclerosis. Adverse reactions to bezafibrate have largely been restricted to gastrointestinal disturbances, with some cutaneous reactions and central nervous system effects. The incidence of side effects has been no greater than with comparative lipid-lowering drugs. In patients with renal disease, a few cases of marked elevation of serum creatine phosphokinase and myoglobin, and associated muscle cramps, have been reported (diagnosed as rhabdomyolysis). Hepatic enzyme induction by bezafibrate in rats results in hepatomegaly, but there has been no case of significant hepatotoxicity in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Definition and management of hyperlipoproteinemia.

The results of recent large, prospective clinical trials have established that the reduction of plasma total and low density lipoprotein cholesterol concentrations in certain hyperlipidemic patients reduced their risk for developing symptomatic cardiovascular disease. Attention has now been turned to both defining which individuals should be treated and how best to treat those patients. Utilizing the concepts of human lipid, lipoprotein, and apolipoprotein metabolism that have evolved over the past 20 years, the metabolism of the plasma lipoproteins can be effectively modulated in the majority of hyperlipoproteinemic patients. In addition to summarizing human lipoprotein metabolism, this article outlines a step-by-step approach to the treatment of hyperlipoproteinemia.

Distribution of cyclosporine in blood of a renal-transplant recipient with type V hyperlipoproteinemia.

A patient with severe type V hyperlipoproteinemia and chronic end-stage renal disease received a renal transplant and therapy with cyclosporine. Concentrations of the drug in plasma as determined by liquid chromatography appeared extraordinarily high for the dose ingested. When we measured the drug in the plasma, plasma cleared by ultracentrifugation, leukocytes, erythrocytes, and whole blood, we found that the high concentrations of cyclosporine were associated with the chylomicrons that always were present in this patient's blood. Cyclosporine added directly to this patient's plasma was less associated with the plasma lipids. Isolated lymphocytes and kidney slices incubated with plasma from this patient bound no more drug than when incubated with nonhyperlipemic plasma containing cyclosporine at a normal therapeutic concentration. We conclude that the cyclosporine associated with the chylomicrons in this patient was not biologically available to either lymphocytes or kidney tissue. We strongly recommend the use of chylomicron-cleared plasma for therapeutic drug monitoring of cyclosporine in type V hyperlipoproteinemic patients.

Morphometric study of human hepatic cell modifications induced by fenofibrate

We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 ± 17.04 × 10 −3 cm 3/cm 3; diet only, 185.84 ± 8.96 10 −3, P < .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 ± 0.03 × 10 10 cm −3; diet only, 0.32 ± 0.08 × 10 10 cm −3, P < .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 ± 1.44 × 10 −3 cm 3/cm 3; diet only, 13.61 ± 1.17 × 10 −3, P < .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.

Systematic analysis of serum lipoproteins and apolipoproteins by a combined technique of micro two‐dimensional electrophoresis

AbstractLipoproteins in human serum and in lipoprotein fractions obtained by sequential ultracentrifugation of serum were analyzed by combining three types of micro two‐dimensional electrophoresis (2‐DE) technique to obtain systematic information on lipoproteins and apolipoproteins. The samples were first analyzed under non‐denaturing conditions of electrophoresis to characterize the physicochemical properties of low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL) under physiological conditions. The samples were then analyzed, employing isoelectric focusing without denaturants in the first dimension and sodium dodecyl sulfate (SDS) electrophoresis in the second dimension, to study the process of dissociation of lipoproteins to apolipoproteins. The HDL's dissociated into their constituent apolipoproteins, showing that the charge heterogeneity of HDL is caused by the heterogeneous apolipoprotein content. LDL dissociated into apo B‐100 and minor components. In the third type of micro 2‐DE, employing urea and Nonidet P‐40 in the first dimension and SDS in the second dimension, the lipoproteins were dissociated into their apolipoproteins during the steps of sample treatment, to obtain the information on the contnt of apolipoprotein peptides and their genetic alleles. The combined micro 2‐DE technique will be useful for the systematic analysis of lipoproteins and apolipoproteins in hypo‐ and hyperlipoproteinemic patients.