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At least 19 recordsLinked to original sources
PubMed1993

Complexoproductive and antiheparin properties of low density lipoproteins (LDL). III. Interaction of low density lipoproteins (LDL) with synthetic polyanionic compounds.

Low density lipoprotein (LDL) form insoluble complex bonds with polymetacrylic and polyvinylsulphonic acids in the presence of calcium chloride. Quantity of arising complexes depends on the concentrations of LDL, acids and calcium chloride and on pH. These complexes dissociate solutions of sodium chloride, urea and guanidine hydrochloride.

Calcium Chloride↗
PubMed1997

Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins during aging: the effects of Q-10 supplementation.

Evidence is rapidly accumulating that oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. In this study we measured the total peroxyl radical trapping capacity of human plasma LDL phospholipids (TRAPLDL) with a luminescent method. The study was carried out with 70 healthy volunteers, aged 28-77. In males an age-related decrease in TRAPLDL was observed. In the age group under 50 years the mean TRAPLDL was 31.36 +/- 1.45 pmol peroxyl radicals/nmol Pi; among those over 50 years it was significantly lower at 26.67 0.94 pmol/nmol Pi. As regards the components of TRAPLDL, the concentration of LDL-ubiquinol did not change and a non-significant decrease in the LDL-tocopherol concentration was detected with age. In females, the mean TRAPLDL, LDL-ubiquinol-10 and tocopherol concentrations did not differ between the age groups. When 17 of the participants were given coenzyme Q10 (Q10) supplementation, 100 mg/day, a highly significant increase in LDL-ubiquinol concentration was detected. Our results indicate that LDL antioxidant defenses tend to decrease with age in the Finnish male population. The decline is most significant in males under 50 years; in older age groups the values remain stable at a low level. Q10 supplementation doubles the number of ubiquinol-10-containing LDL molecules and may therefore have an inhibitory effect on LDL oxidation.

Administration, Oral↗
PubMed1992

Complexoproductive and antiheparin properties of low density lipoproteins (LDL). II. Interaction of serum low density lipoproteins (LDL) with heparin of different molecular weight.

Quantity of unsoluble LDL complexes with heparin of different molecular weight in hypo-, normo-, and hyperlipemic blood serum in the presence of CaCl2 was estimated. At the same weight concentration the biggest quantity of LDL complexes are formed with heparin with heparin of the molecular weight 16000, the quantity is smaller with heparin of the molecular weight 5100, and it is the smallest with heparin of molecular weight 3700.

Calcium Chloride↗
PubMed2000

The effects of isolated lipoproteins and triglyceride, combined oxidized low density lipoprotein (LDL) plus triglyceride, and combined oxidized LDL plus high density lipoprotein on the contractile and relaxation response of rabbit cavernous smooth muscle.

The aim of this study was to investigate the effects of isolated lipoproteins and triglyceride (TG), and the effects of combined oxidized low density lipoprotein (LDL) plus TG and the combined oxidized LDL plus high density lipoprotein (HDL) on the contractility and relaxation response of rabbit cavernous smooth muscle. Cavernous muscle strips from New Zealand White rabbits were studied in organ chambers for isometric tension measurement. The strips were exposed to HDL, LDL, oxidized LDL, TG, combined oxidized LDL plus TG and combined oxidized LDL plus HDL for 30 min. Both HDL and LDL did not affect contraction and relaxation responses of the cavernous muscles. The oxidized LDL did not affect norepinephrine (NE)-induced contractility of the strips, but significantly (p < 0.05) decreased the relaxation response to endothelium-dependent agonist, acetylcholine (Ach). Non-specific NO synthase inhibitor (L-NAME) completely inhibited the relaxation response to Ach, and L-arginine partially improved the diminished relaxation. TG did not significantly change the relaxation responses to Ach, but decreased the contractility of cavernous muscle to NE. Neither the combined oxidized LDL plus TG nor oxidized LDL plus HDL had significant synergistic or detoxication effects on the contractility and relaxation responses. In conclusion, oxidized LDL may have acute toxic effects on the endothelium-dependent, NO-mediated relaxation, but not on the contractility, of rabbit cavernous smooth muscle. TG may decrease contractility of the cavernous muscle. There may be neither synergistic nor detoxication effects on the contractility and relaxation response when TG or HDL is added to the oxidized LDL.

Animals↗
PubMed1988

The effects of phthalimide and saccharin derivatives on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity and related enzyme activities.

The hypolipidemic agents, phthalimide, saccharin, o-(N-phthalimido) acetophenone, N-(p-chlorobenzoyl) sulfamate, and o-chlorobenzylsulfonamide affected low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity and lipoprotein degradation. In isolated rat hepatocytes, rat aorta foam cells, and human fibroblasts, LDL receptor activity, which is dependent on apo-B and -E, was inhibited by the drugs in a dose-dependent manner. LDL degradation was accelerated in the hepatocytes, while it was inhibited in aorta cells and fibroblasts. The drugs enhanced HDL receptor activity, dependent on apo-E and -A1, and HDL degradation in the hepatocytes, whereas in fibroblasts and aorta cells HDL receptor binding and degradation were suppressed. In parallel, activities of acyl CoA acyl transferase, sn-glycerol-3-phosphate acyl transferase, and heparin-induced lipoprotein lipase decreased and activities of HMG-CoA reductase and cholesterol oleate-ester hydrolase increased. In fibroblasts the presence of drugs enhanced HDL binding of intracellular cholesterol. In vivo studies demonstrated that phthalimide and saccharin treatment enhanced the clearance of HDL and decreased the clearance of LDL from the serum of rats. The results suggest that the mode of action of the agents is to modulate the lipoprotein receptor and, thereby, the clearance of lipids from peripheral tissue as part of the hypolipidemic activity.

Animals↗
PubMed2000

Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL.

Low density lipoprotein (LDL) particles are the major cholesterol carriers in circulation and their physiological function is to carry cholesterol to the cells. In the process of atherogenesis these particles are modified and they accumulate in the arterial wall. Although the composition and overall structure of the LDL particles is well known, the fundamental molecular interactions and their impact on the structure of LDL particles are not well understood. Here, the existing pieces of structural information on LDL particles are combined with computer models of the individual molecular components to give a detailed structural model and visualization of the particles. Strong evidence is presented in favor of interactions between LDL lipid constituents that lead to specific domain formation in the particles. A new three-layer model, which divides the LDL particle into outer surface, interfacial layer, and core, and which is capable of explaining some seemingly contradictory interpretations of molecular interactions in LDL particles, is also presented. A new molecular interaction model for the beta-sheet structure and phosphatidylcholine headgroups is introduced and an overall view of the tertiary structure of apolipoprotein B-100 in the LDL particles is presented. This structural information is also utilized to understand and explain the molecular characteristics and interactions of modified, atherogenic LDL particles.

Apolipoprotein B-100↗
PubMed1992

In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL).

Low density lipoproteins (LDL) were isolated by immunoaffinity chromatography from 18 patients (31-70 years) suffering from primary hypercholesterolemia with angiographically proven atherosclerosis of either one or both carotid arteries. LDL were labeled with 123I (1 mCi/mg LDL) by the iodine monochloride method followed by purification with dialysis and immediately reinjected thereafter. Gamma-camera serial controls over carotid regions allowed visual detection of uptake of the radiocompound uptake in 12 out of the 18 patients. The lipid entry ratio (LER; counts over the vascular region/pixel as compared to the contralateral side after background subtraction) confirmed the visual findings. Whole body images performed until 20 h after reinjection showed 3 different kinetic types of LDL-influx into the vessel wall: decreasing (type I), increasing and then decreasing (type II) and continuously increasing (type III) with time. Four patients underwent endarterectomy within 2-7 weeks after gamma-camera imaging. Histological control revealed an extensive amount of "foam cells" in tissue samples derived during surgery and an absence of endothelial lining in samples belonging to patients with type II kinetics.

Adult↗
PubMed1999

[Lowering of resistance to oxidation of VLDL lipoproteins and some subfractions of LDL lipoproteins in patients with non-insulin-dependent diabetes mellitus].

AIM: To investigate composition of very low density lipoproteins (VLDLP) and some subfractions of low density lipoproteins (LDLP), and their resistance to oxidation in patients with non-insulin-dependent diabetes mellitus (NIDDM) varying in severity compared to healthy subjects. MATERIALS AND METHODS: 26 NIDDM patients and 16 healthy controls. VLDLP and subfractions of LDLP were isolated by ultracentrifugation. The lipoproteins were assayed for protein, cholesterol, initial products of lipid peroxidation (LPO). After autooxidation of lipoproteins, fluorimetry examined the degree of the oxidant modification. RESULTS: The initial level of LPO products was elevated in VLDLP and light subfractions of LDLP in severe and moderate NIDDM patients. Even in mild NIDDM, resistance to oxidation of dense LDLP subfractions was low and continued to decrease with aggravation of the disease. High ratio cholesterol/ protein occurred in VLDLP and subfractions of LDLP from patient with severe NIDDM. CONCLUSION: It is shown that subnormal resistance to oxidation of LDLP dense subfractions even in mild NIDDM is an informative diagnostic criterion of risk factor to develop atherosclerosis.

Adult↗
PubMed1999

Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects.

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

Adult↗
PubMed1998

Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles.

Low density lipoprotein (LDL) has been found suitable as a targeting carrier for cytotoxic drugs. However, higher drug loading into LDL particles without disrupting their native integrity remains a major obstacle. The purpose of this study is to investigate the different physicochemical factors that may affect drug loading and to characterize LDL-drug conjugates. Doxorubicin (Dox) and 3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine (dpIUdR) were used as reference cytotoxic drugs. Drugs were loaded into LDL particles using the dry film method with or without surfactants, liposomal and the direct addition method. The effects of incubation temperature, time and stoichiometry of LDL-drug conjugates on drug loading were investigated. The LDL-drug conjugates were evaluated for their stability and characterized by differential scanning calorimetry (DSC), denatured gel (SDS-PAGE), and electron microscopy (EM). We have suitably incorporated 45+/-10 Dox and 150+/-25 dpIUdR molecules/LDL particle. A seven-fold increase in Dox incorporation was achieved with the liposomal preparation compared to the dry film method. A 4- to 6-h incubation at 37 degreesC was suitable to restore the native structure of LDL particles. No apo B fragmentation of LDL particles was noted on denatured gel. DSC studies showed no change in the Tm of the LDL and the LDL-drug conjugates. An increase in particle size of LDL-dpIUdR, not LDL-Dox was observed in EM compared to the native LDL which may be related to higher incorporation of dpIUdR. The results indicate that physicochemical factors significantly affect drug loading efficiency and may need to be considered to optimize drug incorporation into LDL particles.

Chromatography, High Pressure Liquid↗
PubMed1996

Effect of lipid transfer activity and lipolysis on low density lipoprotein (LDL) oxidizability: evidence for lipolysis-generated non-esterified fatty acids as inhibitors of LDL oxidation.

Low density lipoproteins (LDL) were modified in vitro in the presence of lipid transfer activity and lipolysis, which induced alterations in the size and lipid composition of LDL particles but not in their antioxidant content. Subsequently, modified LDL were oxidized with copper sulfate and the extent of LDL oxidation was evaluated. Lipid transfer activity alone, or in combination with lipolysis, led to a significant reduction of LDL oxidability as compared with starting homologous LDL. Furthermore, the combined effect of lipid transfers and lipolysis reduced LDL oxidability to a significantly greater extent than did lipid transfers alone. Consistent results were obtained by measuring either the formation of lipid peroxides, the appearance of thiobarbituric acid reactive substances (TBARS), the disappearance of polyunsaturated fatty acids (PUFA), or the generation of cholesterol oxides. Non-esterified fatty acids (NEFA) arose as putative candidates in reducing oxidation susceptibility of LDL: NEFA-containing LDL were less oxidizable; the enrichment of LDL with either oleic acid or linoleic acid reduced significantly their oxidability; the oxidation susceptibility of either in vitro modified LDL or LDL isolated from normal or analbuminemic patients significantly increased after reduction of their NEFA content with fatty acid-poor albumin. After NEFA depletion, small-sized LDL resulting from the combined effects of lipid transfer and triglyceride hydrolysis activities became more oxidizable than large-sized LDL treated with lipid transfer activity alone. In addition, the PUFA to total fatty acid ratio and the oxidability of modified LDL varied accordingly after NEFA depletion, showing that in the present study not only lipoprotein-bound NEFA but also the total fatty acid composition of LDL could account for alterations in their oxidability.

Chromatography, High Pressure Liquid↗
PubMed1997

Gliclazide decreases cell-mediated low-density lipoprotein (LDL) oxidation and reduces monocyte adhesion to endothelial cells induced by oxidatively modified LDL.

Low-density lipoprotein (LDL) oxidation has been suggested to play a key role in the pathogenesis of atherosclerosis, a major complication of diabetes mellitus. Gliclazide, a second-generation sulfonylurea, is widely used in the treatment of type II diabetes mellitus. Recently, a free-radical-scavenging activity of gliclazide has been reported. In the present study, we examined the effects of gliclazide on cell-mediated LDL oxidation and monocyte adhesion to endothelial cells induced by oxidatively modified LDL. Incubation of human monocytes and bovine aortic endothelial cells (BAE cells) with increasing concentrations of gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) resulted in a dose-dependent diminution of cell-mediated LDL oxidation as assayed by measurement of thiobarbituric acid (TBA)-reactive substances (TBARS). In addition, exposure of BAE cells to gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) induced a dose-dependent diminution of the oxidized LDL-induced monocyte adhesion to BAE cells as measured by the myeloperoxidase (MPO) assay. The effects of glyburide, another second-generation sulfonylurea, were also tested on cell-mediated oxidation of LDL and LDL-induced monocyte adhesion to the endothelium. No significant effect of this drug was observed on these two processes. These results therefore demonstrate that gliclazide is effective in vitro in reducing both cell-mediated LDL oxidation and monocyte adhesion to the endothelium. These findings suggest a potential beneficial effect of gliclazide in the prevention of atherosclerosis in diabetic patients.

Animals↗
PubMed1988

Hormonal regulation of low-density lipoprotein (LDL) receptor activity in human hepatoma Hep G2 cells. Insulin increases LDL receptor activity and diminishes its suppression by exogenous LDL.

Low-density lipoprotein (LDL) receptors of approximate Mr 130,000 on non-reduced gels have been identified in Hep G2 cells by immuno- and ligand-blotting of cell extracts. Measurement of LDL receptor protein by scanning ligand blots was correlated with the specific binding, uptake and degradation of 125I-labelled LDL by intact cells, confirming that this is mediated by the LDL receptor. Cells incubated in medium with serum expressed significant LDL receptor activity. This increased when cells were transferred to medium containing lipoprotein-deficient serum (LPDS) but was not maximal because a further increase occurred when compactin was included in the medium. Inclusion of 17 alpha-ethinyl estradiol or 17 beta-estradiol in the medium at concentrations up to 500 ng/ml had no effect on LDL receptor activity in the cells as assayed by ligand blotting. Inclusion of insulin (100 mU/ml) in the preincubation medium containing LPDS resulted in a twofold increase in LDL-receptor protein and of LDL binding and degradation by intact cells. Insulin also diminished the suppressive effect of LDL on LDL receptor activity. If insulin exerts this effect in vivo it may partly explain why the liver expresses LDL receptors despite high levels of LDL in plasma and interstitial fluid.

Carcinoma, Hepatocellular↗
PubMed1986

Plasma high density lipoprotein is increased in man when low density lipoprotein (LDL) is lowered by LDL-pheresis.

Plasma high density lipoprotein (HDL) concentrations were increased in five hypercholesterolemic normoglyceridemic patients after removal of plasma low density lipoprotein (LDL) by LDL-pheresis. In each patient up to 80% of circulating LDL was removed by passing plasma through immunoadsorption columns containing antibody to apolipoprotein B immobilized to Sepharose. Rebound of LDL was slow after the procedure: 5-7 days in four non-familial hypercholesterolemic patients and greater than 14 days in one patient with homozygous familial hypercholesterolemia. Plasma HDL rose above the pretreatment baseline during the interval between treatments in four of the five patients. When treatments were repeated weekly, time-averaged plasma LDL was lowered by 40-70%, while plasma HDL cholesterol and apolipoprotein AI were increased up to 2-fold, depending on the degree of LDL lowering. Plasma HDL concentrations fell back to their baseline values when LDL-pheresis was stopped and rose again when treatment was restarted. Thus, LDL-pheresis may augment the therapeutic effectiveness of LDL lowering by raising plasma HDL levels and the concentration of HDL relative to LDL.

Adult↗
PubMed1979

Uptake and degradation of low density lipoproteins (LDL) by confluent, contact-inhibited bovine and human endothelial cells exposed to physiological concentrations of LDL.

Metabolism of low density lipoproteins (LDL) was studied in cultures of endothelial cells derived from bovine aorta or heart and from human umbilical veins. At low LDL concentrations nonconfluent cultures of bovine endothelial cells catabolized more LDL protein than contact-inhibited confluent cultures but this difference was reduced at high LDL concentrations. Nonconfluent human endothelial cells displayed also a higher rate of LDL degradation than their contact-inhibited counterparts, but this difference was less pronounced than in the bovine cells. Bovine endothelial cells grown in the presence of fibroblast growth factor metabolized less LDL than those cultured without fibroblast growth factor (FGF), but this difference was not consistent in the human endothelial cells. The data presented provide evidence that contact-inhibited confluent human endothelial cells are capable of catabolizing LDL when exposed to physiological concentrations of this lipoprotein.

Animals↗
PubMed1997

Corticotropin increases the receptor-specific uptake of native low-density lipoprotein (LDL)--but not of oxidized LDL and native or oxidized lipoprotein(a) [Lp(a)]--in HEPG2 cells: no evidence for Lp(a) catabolism via the LDL-receptor.

To understand the interaction of corticotropin (ACTH) and lipid catabolism, we analyzed the influence of ACTH on receptor-mediated lipoprotein uptake and compared the uptake and degradation of human native (N-LDL) and oxidized (Ox-LDL) low-density lipoprotein and native (N-Lp(a)) and oxidized (Ox-Lp(a)) lipoprotein(a) by human hepatoma (HepG2) cells. The receptor affinity of N-LDL, Ox-LDL, N-Lp(a), and Ox-Lp(a) was comparable (Kd, 33, 13, 24, and 13 micrograms/mL medium), whereas the maximum degradative capacity was 10.5-fold higher in N-LDL (Vmax, 1,978 ng/mg cell protein) compared with Ox-LDL (189 ng/mg). In N-LDL, it was 4.5-fold higher than in N-Lp(a) (442 ng/mg) and eightfold higher than in Ox-Lp(a) (246 ng/mg) (P < .05). Addition of ACTH to the cell cultures increased receptor-specific degradation of N-LDL by 44% (2,866 v 1,978 ng/mg, P < .05), whereas changes in Ox-LDL, N-Lp(a), and Ox-Lp(a) showed no significant increase. No differences in uptake specificity were observed with or without ACTH. In addition, a 12-hour preincubation of liver cells with LDL increased Lp(a) uptake by 40% to 50% with (411 v 620 ng/mg) and without (393 v 558 ng/mg) ACTH administration. These data indicate that ACTH elevates receptor-specific uptake of N-LDL, but only to a low extent versus Ox-LDL, N-Lp(a), or Ox-Lp(a). These results support the hypothesis that catabolism of oxidized lipoproteins and Lp(a) through the LDL receptor pathway is only a minor route of lipid metabolism, whereas LDL receptor activity itself can be stimulated by ACTH.

Adrenocorticotropic Hormone↗