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At least 19 recordsLinked to original sources
PubMed1991

Influence of early diabetic nephropathy on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition.

The procedure of discontinuous gradient ultracentrifugation (DGU) was used to characterize the influence of early diabetic nephropathy on the composition of very low density lipoprotein (VLDL, flotation density 60-400 Svedberg (Sf) units), low density lipoprotein (LDL, flotation density 0-12 Sf) and subfractions of intermediate density lipoprotein (IDL1 and IDL2, 20-60 and 12-20 Sf, respectively). Forty-six subjects with type 1 (insulin-dependent) diabetes and serum creatinine, less than 140 mumol/l were studied, of whom 23 consistently had normal rates of albumin excretion (AER less than 15 micrograms/min), and 23 had persistent albuminuria (AER 20.0-960.6 micrograms/min). The two groups were similar with respect to total serum lipids, glycaemic control, age and body mass. The composition (lipid, protein and phospholipid) and mass of VLDL, LDL and IDL2 was not appreciably altered by early nephropathy, but free and total cholesterol concentration in IDL1 (Sf 20-60) was increased (total cholesterol 0.68 (0.09) (mean (SE)) vs. 0.47 (0.07) mmol/l, and free cholesterol 0.27 (0.04) vs. 0.17 (0.03) mmol/l, both P less than 0.05). The explanation of these findings was probably an accumulation in the circulation of the remnants of chylomicron metabolism and/or intermediates in the conversion from VLDL to IDL1. In addition, there was a decrease in serum high density lipoprotein (HDL) cholesterol in early nephropathy (1.27 (0.06) vs. 1.38 (0.10) mmol/l, P less than 0.05), due to a decrease in the HDL2 cholesterol subfraction (P less than 0.05). These findings may in part explain the increased risk of premature atherosclerosis associated with the development of albuminuria.

Adolescent↗
PubMed1992

The effect of bezafibrate on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition in type 1 diabetes associated with hypercholesterolaemia or combined hyperlipidaemia.

Lipoprotein composition was examined in type 1 diabetic subjects with hypercholesterolaemia +/- hypertriglyceridaemia during a 3-month double-blind placebo controlled assessment of bezafibrate therapy. The predominant effect was on lipoprotein lipid content. In those with hypercholesterolaemia alone, bezafibrate significantly reduced the cholesterol (particularly esterified cholesterol) and triglyceride content of large very low density lipoprotein (VLDL) (Svedberg flotation units (Sf) 60-400) in comparison to the placebo group (P less than 0.05), and a trend towards a reduction in free and esterified cholesterol within the intermediate density lipoprotein fraction (IDL) (Sf 12-20) was noted. Low density lipoprotein (LDL) composition was unaltered and in general phospholipid and protein concentrations and cholesteryl ester/protein ratios within the lipoprotein fractions were unaffected. Large VLDL cholesterol and triglyceride concentrations in those with combined hyperlipidaemia were significantly decreased following bezafibrate therapy, both in comparison to placebo-treated subjects and to baseline concentrations (P less than 0.05). An additional significant reduction in small VLDL (Sf 20-60) free cholesterol was recorded (P less than 0.05). Average reductions of large and small VLDL protein of 50-56% were not significant because of wide variation in responses. Bezafibrate had no effect on the abnormal composition of IDL and LDL, characteristic of Type 1 diabetes, regardless of whether or not hypertriglyceridaemia was associated with hypercholesterolaemia. Its major action was to lower VLDL lipid concentrations, but it may also reduce the lipid content of intermediate density lipoprotein in Type 1 diabetes.

Adolescent↗
PubMed1986

Stimulating effect of intermediate-density lipoproteins (IDL) from hyperlipemic plasma on hepatic lipase.

The main lipoprotein density classes, namely very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 were investigated with respect to their influence on hepatic lipase (HTGL) activity in vitro. Lipoproteins from pooled normal plasma (NP) and from pooled hyperlipemic plasma (HP) were prepared by means of sequential ultracentrifugation. Hepatic lipase was determined radioenzymatically after preincubation with protamine sulfate. It could be demonstrated that IDL from HP were able to stimulate HTGL activity by approximately 100% above the baseline value. HDL3 from both NP and HP revealed an inhibiting effect on HTGL activity. VLDL, LDL, and HDL2 exhibited no significant effect on HTGL activity. It is speculated that HTGL could possibly represent a second pathophysiological pathway for the catabolism of IDL in hyperlipemia but this presumption is supported by only a few investigations in vivo.

Cholesterol↗
PubMed1990

Cellular metabolism of human plasma intermediate-density lipoprotein (IDL).

The cellular metabolism of human plasma intermediate-density lipoprotein (IDL) was investigated in cultured human skin fibroblasts and hepG-2 cell in the absence and presence of exogenous recombinant or plasmatic apo E-3. IDL (d 1.006-1.019 g/ml) and LDL (d 1.019-1.063 g/ml) were prepared by centrifugation from the plasma of apo E-3/3 or 4/3 normolipidemic human subjects. Without added apo E-3, IDL binding and cell association are similar or slightly reduced while their degradation is one third to one half. This results in degradation to binding ratios for IDL that are half those for LDL. Exogenous apo E-3 enhances binding, association and degradation of IDL by 50-150%, but the degradation to binding ratio remains low. Exogenous apo E-3 also increased the ability of IDL but not LDL, to down-regulate the incorporation of [14C]acetate to sterol by the cells. The optimal concentration of apo E-3 is 4 micrograms protein/10 micrograms IDL protein and at that concentration appreciable amounts of the apo E are found associated with the lipoprotein. Apo E-2 has no effect on the cellular metabolism of IDL and apo E-3 is not effective in receptor-negative human fibroblasts. Monoclonal antibodies that block apo E binding to B,E (LDL) receptor (1D7) abolish the cellular metabolism of IDL while antibodies against B-100 (4G3) are ineffective. In competitive binding experiments, IDL is slightly more effective than LDL in displacing 125I-LDL from receptors in hepG-2 cells and appreciably more effective than LDL when tested against 125I-IDL. Apo E-3 increases the capacity of IDL to compete with either 125I-LDL or 125I-IDL. Addition of apo E-3 also increases the binding affinity of IDL to hepG-2 receptors, with Kd values of 2.50, 0.93 micrograms protein/ml, respectively. The study demonstrates the essential role that functional apo E molecules play in the interaction of human IDL with cellular receptors. Yet, in spite of presence of apo E in IDL (2-3 molecules/particle) and enrichment of IDL with apo E-3 (to 4-5 molecules/particle) the proteolytic degradation of the lipoprotein by specific cellular receptor is similar to LDL.

Antibodies, Monoclonal↗
PubMed2000

Hyperapobetalipoproteinemia with compositional abnormality of LDL and IDL, a characteristic lipoprotein alteration in essential hypertension.

The number and composition of apoprotein B (apoB)-containing lipoproteins that are very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) have been analyzed in subjects with essential hypertension who have no obesity and glucose intolerance. Twenty-three essential hypertensive subjects without diabetes mellitus and obesity were recruited. VLDL, IDL, LDL, and high-density lipoprotein (HDL) were separated by ultracentrifugation in the 23 hypertensive and 17 healthy subjects (control group). ApoB was determined by highly sensitive latex agglutination method in each lipoprotein fraction. There were no significant differences in age and body mass index between the hypertension and control groups. In hypertension, cholesterol levels significantly increased in plasma (13%, P < .05) and in LDL (20%, P < .05), but decreased in HDL (-14%, P < .05). Triglyceride significantly increased in plasma (66%, P < .05) and in VLDL (105%, P < .05). ApoB also significantly increased in plasma and all lipoprotein fractions except HDL. (plasma, 35%; VLDL, 94%; IDL, 82%; LDL, 42%; P < .05). With respect to lipoprotein composition, the ratio of cholesterol to apoB significantly decreased in IDL (P < .05) and LDL (P < .05). In essential hypertension, the number of apoB-containing lipoproteins (VLDL, IDL, LDL) all increased. A low ratio of cholesterol to apoB without changes in the ratio of triglyceride to apoB was noted in IDL and LDL, indicating the presence of small dense lipoprotein particles. Characteristic disorders of pure essential hypertension are characterized by hyperapobetalipoproteinemia and small dense LDL.

Biomarkers↗
PubMed1998

The very low- and intermediate-density lipoprotein fraction isolated from apolipoprotein E-knockout mice transforms macrophages to foam cells through an apolipoprotein E-independent pathway.

Apolipoprotein E (apoE)-knockout mice develop severe atherosclerosis associated with high levels of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) in plasma. To investigate the atherogenic role of VLDL and IDL, the lipoprotein fraction containing both VLDL and IDL (apoEko-VLDL/IDL) was isolated from plasma of apoE-knockout mice by ultracentrifugation, and its interaction with macrophages was studied. When peritoneal macrophages obtained from apoE-knockout mice were incubated with apoEko-VLDL/IDL, the level of cellular cholesteryl esters (CE) increased with the concentration of apoEko-VLDL/IDL. The level of cellular cholesteryl [3H]oleate formed reached 15.1 nmol/mg of cell protein upon incubation with 50 microg/mL apoEko-VLDL/IDL for 18 h, which was an 8.4-fold increase over the corresponding level induced by low-density lipoprotein (LDL). The cellular CE mass was also significantly increased by apoEko-VLDL/IDL. Morphologically, after exposure to apoEko-VLDL/IDL, macrophages became strongly stained with Sudan black B. The total binding of [125I]apoEko-VLDL/IDL to macrophages was effectively replaced by more than 80% by an excess of the unlabeled ligand. Specific binding, calculated by subtracting the nonspecific binding from the total binding, exhibited a saturation pattern. Similar results were obtained with cell association and degradation experiments. In addition, the endocytic degradation of [125I]apoEko-VLDL/IDL was partially inhibited by LDL, whereas acetyl-LDL did not show any effect. These results indicated that apoEko-VLDL/IDL in its unmodified form produced significant CE accumulation in macrophages through a specific and apoE-independent pathway. This pathway may explain, in part, the mechanisms of foam cell formation in arterial walls and the subsequent development of atherosclerosis in apoE-knockout mice.

Animals↗
PubMed1981

Intermediate-density lipoprotein and cholesterol-rich very low density lipoprotein in angiographically determined coronary artery disease.

The relationship between the concentrations of intermediate-density lipoprotein (IDL) and other lipoproteins and the extent of coronary artery disease (CAD) was studied in 182 consecutive patients evaluated by selective coronary cineangiography. On univariate analysis, the extent of CAD correlated significantly and positively with very low density lipoprotein (VLDL) cholesterol, IDL cholesterol and low-density lipoprotein (LDL) cholesterol, and negatively with high-density lipoprotein (HDL) cholesterol. Analysis of four subgroups divided by IDL cholesterol and LDL cholesterol levels indicated that moderately increased levels of IDL cholesterol were closely associated with a high frequency of CAD. Moreover, multi-variate regression analysis demonstrated that IDL cholesterol for men, LDL cholesterol for men and women and HDL cholesterol for men were significant variables of use in the final weighting procedure. IDL cholesterol was closely associated with cholesterol-rich VLDL. This study shows that IDL and cholesterol-rich VLDL combine to contribute to the development of CAD.

Adult↗
PubMed1999

Apolipoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipidemic (SMHL) rabbit.

The St. Thomas' mixed hyperlipidemic (SMHL) rabbit (previously St. Thomas' Hospital rabbit) is a putative model of familial combined hyperlipidemia (FCH). When fed a low (0.08%) cholesterol diet, it exhibits elevations in both plasma cholesterol and triglyceride compared to New Zealand White (NZW) controls. To determine the mechanism for this hyperlipidemia we studied the secretion of apolipoprotein B (apoB)-containing lipoproteins from perfused livers of both young and mature rabbits. During a 3-h perfusion we measured the total cholesterol and triglyceride content of the medium and the cholesterol, triglyceride, and apoB content of very low density lipoprotein (VLDL)(1) (S(f) 60;-400), VLDL(2) (S(f) 20;-60), intermediate (S(f) 12;-20), and low (S(f) 0;-12) density lipoproteins (IDL, LDL). Lipoprotein concentrations increased linearly throughout the perfusion period. The rate of cholesterol output was 3-fold higher (459 vs. 137 ng/g liver/min, P = 0.003) in SMHL versus NZW rabbits whilst that of triglyceride was similar (841 vs. 662 ng/g liver/min, NS). VLDL(1) cholesterol output was elevated 2-fold (232 vs. 123 ng/g liver/min, P < 0.05) and VLDL(2) + IDL + LDL cholesterol output, 4.5-fold (106 vs. 23 ng/g liver/min, P < 0. 005) in SMHL versus NZW rabbits. ApoB output in VLDL1 was 38 ng/g liver per min in SMHL and 14 ng/g liver per min in NZW (NS). In SMHL VLDL(2) + IDL + LDL apoB was increased 9-fold at 53 versus 6 ng/g liver per min in NZW (P < 0.001). We conclude that the SMHL rabbit overproduces apoB-containing lipoproteins particularly in the VLDL(2) + IDL + LDL fraction, a characteristic consistent with its use as a model of FCH.

Animals↗
PubMed1991

The tangled web of coronary risk factors.

Although epidemiologic, genetic, and pathophysiologic studies have shown that low-density lipoproteins (LDLs) are involved in the development of coronary artery disease, the standard measurement of LDL cholesterol comprises a number of separate components that may contribute in different ways to the disease process. Some of these components appear to be of particular pathologic importance. Intermediate-density lipoproteins (IDLs) and lipoprotein (a) are highly atherogenic species that each normally account for up to 10% to 15% total LDL cholesterol but may be disproportionately elevated in pathologic states and may therefore contribute disproportionately to coronary disease risk in certain patients. Recently, another subclass of LDL, characterized by relatively small particle size and increased density, also has been found to be associated with relatively increased risk of coronary disease. Furthermore, levels of this subclass, designated LDL-III, are linked to a number of interrelated hormonal and metabolic factors, each of which have also been associated with risk of coronary artery disease. These include male gender, postmenopause, abdominal adiposity, elevated triglyceride levels, increased levels of apolipoprotein B, and reductions in high-density lipoproteins (HDLs), particularly in the HDL2 subclass. Other studies have demonstrated that many of these factors are also commonly associated with relative insulin resistance and hyperinsulinemia. Thus, a lipoprotein profile characterized by a relative increase in LDL-III and a reduction in HDL2 is indicative of a constellation of metabolic features that defines a high-risk state and that makes it extremely difficult to single out one or more factors that are most directly involved in the disease process. Combinations of genetic and environmental factors acting on this "tangled web" of risk factors may account for much of the variation in coronary disease susceptibility found in the general population.

Androgens↗
PubMed1999

Effects of cholesterol-lowering treatments on oxidative modification of plasma intermediate density lipoprotein plus low density lipoprotein fraction in Type 2 diabetic patients.

To investigate the normalization of enhanced oxidative modification of the lipoprotein such as increased lysophosphatidylcholine (LPC) and lipid hydroperoxide (LPO) contents in diabetic subjects, we studied the effect of cholesterol-lowering treatment on those parameters in 24 hypercholesterolemic Type 2 diabetic patients. Those patients were randomly assigned to two treatment groups, such as 12 patients treated with pravastatin 10 mg daily and 12 patients treated with probucol 500 mg daily for 8 weeks. Characteristics of the patients including age, gender, body mass index (BMI), smoking habit, modality of diabetic treatment and the glycemic control state were comparable between the two groups. LPC content in the lipoprotein fractions obtained from 24 patients with Type 2 diabetes mellitus was significantly higher than that of non-diabetic control subjects. The abnormality was improved to the control level after a significant improvement of serum cholesterol levels following 8 week-treatments with either probucol or pravastatin without any change in glycemic control (P < 0.025). Furthermore, increased LPO content in the lipoprotein fraction in those diabetics was also significantly (P < 0.0025) improved by the probucol treatment and tended to be improved by pravastatin treatment (P = 0.06). LPC contents in the lipoprotein fraction was positively correlated with LPO contents before cholesterol-lowering treatments (r = 0.41, P < 0.05). These results indicate that cholesterol-lowering treatments effectively reduce oxidative modification of the lipoprotein fraction containing intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) in hypercholesterolemic Type 2 diabetic patients.

Anticholesteremic Agents↗
PubMed1993

Effects of lovastatin on the levels, structure, and atherogenicity of VLDL in patients with moderate hypertriglyceridemia.

The purpose of this study was to determine whether lovastatin treatment reduced very low density lipoprotein (VLDL) abnormalities in hypertriglyceridemic subjects. Lovastatin reduced plasma triglyceride levels and the levels of total VLDL, intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol. The numbers of VLDL particles of Sf 100-400 and Sf 60-100 but not Sf 20-60 particles were reduced by lovastatin, as was the amount of cholesteryl ester per particle. All VLDL subspecies bound to the LDL receptor of cultured human fibroblasts with similar, high affinities on both placebo and lovastatin, but VLDL Sf 100-400 and VLDL Sf 60-100 caused less suppression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase activity after lovastatin therapy, indicating reduced LDL receptor-mediated cholesterol delivery. The average decrease in reductase suppression by VLDL Sf 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL Sf 100-400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL Sf 100-400-induced rapid, receptor-mediated triglyceride accumulation in P388D1 macrophages after lovastatin. Taken together, these observations suggest that lovastatin may be of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.

Adult↗
PubMedDate not supplied

Expression of apolipoprotein B epitopes in lipoproteins. Relationship to conformation and function.

The immunochemical properties of apolipoprotein (apo) B have been studied in very low density lipoprotein (VLDL)1 (Sf 100 to 400), VLDL2 (Sf 60 to 100), VLDL3 (Sf 20 to 60), different intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) subfractions isolated from patients with type IV hypertriglyceridemia. In these lipoproteins, we characterized the association of apo B with other apolipoproteins and the expression and immunoreactivity of several apo B epitopes close to the apo B receptor binding sites (3F5, 4G3, 3A8, and 5E11) and of other epitopes located on the apo B100-B48 common region (1D1 and 2D8). Immunoprecipitation showed that the proportion of lipoprotein particles expressing each apo B epitope increased from VLDL1 to LDL2; this was more apparent with 3A8 and 5E11 than with 3F5. The VLDL that were negative for apo E epitopes (60% or more of the total) were enriched in apo C. The lipoprotein particles containing apo E and/or apo C-III decreased progressively from VLDL1 (30% and 85%, respectively) to LDL2 (10% and 25%, respectively). Similar observations were made for apo C-I and apo D, demonstrating that apolipoprotein heterogeneity is greatest in the lightest lipoproteins. By competitive radioimmunoassay, the epitope for 4G3 was equally immunoreactive in each lipoprotein subclass, and the affinity constant (Ka) of 4G3 for different lipoproteins showed little variation. In contrast, both immunoreactivity and Ka of 3A8 and 5E11 increased progressively and significantly with the increasing density of the lipoprotein subclasses. This phenomenon is correlated with the increasing binding affinity of apo B in these lipoprotein subclasses to the LDL receptor of fibroblasts. We conclude that, as the apo B-containing lipoproteins become smaller, the conformation of specific regions of apo B is modified: in the receptor binding domain, the conformation of epitope 4G3, which is mapped between residues 2980 and 3080, remains constant, while that of 3A8 and 5E11 (residues 3441 to 3568) changes progressively. We propose the theory that the change in conformation in the domain spanning residues 3441 and 3568 allows the maximum expression of epitopes 3A8 and 5E11 and of the receptor binding site.

Adult↗
PubMed1997

Apolipoprotein B (apoB) concentrations in lipoproteins in cows.

The concentrations of apolipoprotein B (apoB)-48 and apoB-100 in triglyceride-rich lipoproteins (TRL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) fractions separated by gel permeation chromatography were determined in Holstein and Japanese black cows by enzyme-linked immunosorbent assay (ELISA). A significant correlation (p < 0.01) was observed between apoB-48 in TRL and plasma triglyceride (TG) levels in both Holstein and Japanese black cows. Additionally, apoB-48 in TRL and plasma TG levels in Holstein cows were significantly lower (p < 0.01) than those in Japanese black cows. These results suggested that TG derived from intestinal (exogenous) TRL rather than from liver (endogenous) TRL was the major source of milk fat.

Animals↗
PubMed2000

Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common inherited hyperlipidemia and a major risk factor for atherothrombotic cardiovascular disease. The cause(s) leading to FCHL are largely unknown, but the existence of unidentified "major" genes that would increase VLDL production and of "modifier" genes that would influence the phenotype of the disease has been proposed. Expression of apolipoprotein A-II (apoA-II), a high density lipoprotein (HDL) of unknown function, in transgenic mice produced increased concentration of apoB-containing lipoproteins and decreased HDL. Here we show that expression of human apoA-II in apoE-deficient mice induces a dose-dependent increase in VLDL, resulting in plasma triglyceride elevations of up to 24-fold in a mouse line that has 2-fold the concentration of human apoA-II of normolipidemic humans, as well as other well-known characteristics of FCHL: increased concentrations of cholesterol, triglyceride, and apoB in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL), reduced HDL cholesterol, normal lipoprotein lipase and hepatic lipase activities, increased production of VLDL triglycerides, and increased susceptibility to atherosclerosis. However, FCHL patients do not have plasma concentrations of human apoA-II as high as those of apoE-deficient mice overexpressing human apoA-II, and the apoA-II gene has not been linked to FCHL in genome-wide scans. Therefore, the apoA-II gene could be a "modifier" FCHL gene influencing the phenotype of the disease in some individuals through unkown mechanisms including an action on a "major" FCHL gene. We conclude that apoE-deficient mice overexpressing human apoA-II constitute useful animal models with which to study the mechanisms leading to overproduction of VLDL, and that apoA-II may function to regulate VLDL production.

Animals↗
PubMed2001

Lipid abnormalities in chronic renal failure, nephrotic syndrome and dialysis.

Cardiovascular, cerebrovascular and peripheral vascular development are the largest cause-specific reason for morbidity and mortality in end-stage renal disease (ESRD) patients. The high prevalence of cardio- and cerebrovascular death may be explained by multiple factors present in patients with progressive renal disease, including hypertension, hyperlipidemia, hyperhomocysteinemia, diabetes mellitus, and hyperparathyroidism. Experimental studies have provided in vivo and in vitro data to support the notion that lipid abnormalities contribute to glomerular and interstitial injury of the renal parenchyma. Hyperchlolesterolemia and increased low-density lipoprotein (LDL) cholesterol are prevalent in patients with the nephrotic syndrome. Plasma high-density lipoprotein (HDL) cholesterol is decreased, and reverse cholesterol transport is impaired in hemodialysis (HD) and pre-ESRD patients. Chronic renal failure patients treated with HD have an increased prevalence of intermediate-density lipoprotein (IDL), and lipoprotein(a). The findings in diabetic patients corresponded with those in nondiabetic patients with renal failure, but diabetic patients have higher apoliprotein C-III and apoliprotein E concentrations. Impaired lipid metabolism is common in patients receiving peritoneal dialysis (PD). In most ESRD patients treated with peritoneal dialysis hypercholesterolemia and hyperglyceridemia are found. Wide panels of therapeutic interventions aimed at correcting the lipid abnormalities that may develop in chronic renal patients as well as in ESRD patients are currently available. Although some novel pharmacological agents are remarkably effective in returning the lipid abnormalities to normal, there is still no convincing evidence based on long-term prospective studies, that would clearly demonstrate a significant reduction of cardiovascular morbidity and mortality of ESRD patients. The therapeutic approaches, which may be considered, include mainly dietary and life-style modifications, selective use of some technical components of dialysis systems, and the judicious prescriptions of lipid-lowering drugs.

Humans↗
PubMedDate not supplied

[Lipoprotein disorders in chronic kidney failure, nephrotic syndrome and dialysis].

Cardiovascular, cerebrovascular and peripheral vascular diseases are the largest cause-specific reason for morbidity and mortality in end-stage renal disease (ESRD) patients. High prevalence of cardio- and cerebrovascular death may be explained by multiple factors present in patients with progressive renal disease, including hypertension, hyprelipidemia, hyperhomocysteinemia, diabetes mellitus, and hyperparathyroidism. Experimental studies have provided in vivo and in vitro data to support the notion that lipid abnormalities contribute to glomerular and interstitial injury of the renal parenchyma. Hypercholesterolemia and increased low-density lipoprotein (LDL) cholesterol are prevalent in patients with the nephrotic syndrome. Plasma high-density lipoprotein (HDL) cholesterol is decreased, and reverse cholesterol transport is impaired in hemodialysis (HD) and pre-ESRD patients. Chronic renal failure patients treated with HD have an increased prevalence of intermediate-density lipoprotein (IDL), and lipoprotein(a). The findings in the diabetic patients corresponded to those in non-diabetic patients with renal failure, but diabetic patients have higher apolipoprotein C-III and apolipoprotein E concentrations. Impaired lipid metabolism is common in patients receiving peritoneal dialysis (PD). In the most of the ESRD patients treated with peritoneal dialysis hypercholesterolemia and hypertriglyceridemia are found. Wide panels of therapeutic interventions aimed at correcting the lipid abnormalities that may develop in chronic renal patients, as well as in ESRD patients are currently available. Although some novel pharmacological agents are remarkably effective for returning the lipid abnormalities to normal, there is still no convincing evidence based on long-term prospective studies which clearly demonstrate a significant reduction in cardiovascular morbidity and mortality of ESRD patients. The therapeutic approaches, which may be considered, include mainly dietary and life-style modifications, selective use of some technical components of dialysis systems, and the judicious prescriptions of lipid-lowering drugs.

Humans↗
PubMed1990

Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production.

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using 125I-labeled VLDL and 131I-labeled LDL and compartmental modeling, before and during lovastatin treatment. Lovastatin therapy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg/dl, P less than 0.0005) and apoB (1328 vs 797 micrograms/ml, P less than 0.001). Before treatment, CHL patients had high production rates (PR) of LDL apoB. Three-fourths of this LDL apoB flux was derived from sources other than circulating VLDL and was, therefore, defined as "cold" LDL apoB flux. Compared to baseline, treatment with lovastatin was associated with a significant reduction in the total rate of entry of apoB-containing lipoproteins into plasma in all seven CHL subjects (40.7 vs. 25.7 mg/kg.day, P less than 0.003). This reduction was associated with a fall in total LDL apoB PR and in "cold" LDL apoB PR in six out of seven CHL subjects. VLDL apoB PR fell in five out of seven CHL subjects. Treatment with lovastatin did not significantly alter VLDL apoB conversion to LDL apoB or LDL apoB fractional catabolic rate (FCR) in CHL patients. In three patients with familial hypercholesterolemia who were studied for comparison, lovastatin treatment increased LDL apoB FCR but did not consistently alter LDL apoB PR. We conclude that lovastatin lowers LDL cholesterol and apoB concentrations in CHL patients by reducing the rate of entry of apoB-containing lipoproteins into plasma, either as VLDL or as directly secreted LDL.

Adult↗
PubMed1994

Ultracentrifugal subclasses of low and intermediate density lipoproteins.

Low density lipoprotein (LDL) and intermediate density lipoprotein (IDL) classes have been shown to be composed of discrete metabolic entities or subclasses. Present ultracentrifugal methods are unable to precisely determine these subclasses. A new analytical micro-ultracentrifugal method was developed that facilitates the determination of IDL and LDL subclasses and their F1.21 flotation coefficient from ultracentrifugal scans. The method is based on the modification of a published equation (Fujita, H. 1956. J. Chem. Phys. 24: 1084-1090) adapted to calculate concentration gradient boundary curves for IDL and LDL that are approximately Gaussian in form. Using an extension of this modified equation, theoretical distributions of the gradient curves were calculated. By applying the theoretical distributions, IDL and LDL subclasses were resolved from absorbance scans as Gaussian concentration gradient boundary curves. Both theoretically calculated and experimentally determined boundary curves for IDL and LDL lipoproteins were plotted and found to be in excellent agreement. Three subclasses of LDL and four subclasses of IDL were determined. The mean flotation rates of the LDL subclasses were: LDL1 = 37.2 +/- 0.6, LDL2 = 31.1 +/- 0.9, and LDL3 = 26.7 +/- 0.7. The mean flotation rates of the IDL subclasses were: IDL1 = 61.6 +/- 0.9, IDL2 = 53.9 +/- 1.0, IDL3 = 50.1 +/- 0.6, and IDL4 = 45.6 +/- 1.1.

Chemical Phenomena↗