Human Serum Low Density Lipoprotein Research Articles

Correlation between serum soluble ASGR1 concentration and low-density lipoprotein cholesterol levels: a cross-sectional study

BackgroundRecent studies have shown that loss-of-function mutations in hepatic asialoglycoprotein receptor 1 (ASGR1) are associated with low levels of circulating cholesterol and a reduced risk of coronary artery disease (CAD). In contrast to ASGR1 on the hepatocyte membrane, serum soluble ASGR1 (sASGR1) is a secreted form that has been detected in circulation. However, the functions of serum sASGR1 are unclear. This study aims to investigate the relationship between human serum sASGR1 concentration and low-density lipoprotein cholesterol (LDL-C) levels.MethodsIn a cohort of 134 participants who underwent coronary angiography examination, basic information was recorded, and blood samples were collected for biochemical testing. The serum sASGR1 concentration was determined by ELISA kits. The relationship between sASGR1 concentration and LDL-C levels was examined using linear regression models and interaction tests. Univariate and multivariate analyses were used to identify clinical variables that affect sASGR1 levels.ResultsAfter adjusting for potential confounders such as age, sex, BMI, and statin use, the serum sASGR1 concentration was positively correlated with LDL-C levels (β = 0.093, 95% CI: 0.04 to 0.14, P < 0.001). Subgroup analysis and interaction tests showed that the effect of serum sASGR1 concentration on LDL-C levels was significantly influenced by hypertension status (P for interaction = 0.0067). The results of a multivariate linear regression analysis incorporating age, serum TG, LDL-C, nonesterified fatty acid (NEFA), white blood cell counts (WBCC), and fibrinogen revealed that LDL-C (β = 1.005, 95% CI: 0.35 to 1.66, P = 0.003) and WBCC (β = 0.787, 95% CI: 0.41 to 1.16, P < 0.0001) were independent influencing factors for serum sASGR1 levels.ConclusionsThe serum sASGR1 concentration was positively correlated with LDL-C levels. In addition, hypertension status significantly affected the effect of serum sASGR1 on LDL-C levels. This study provides some research ideas for clinical doctors and researchers, as well as some references for additional research on serum sASGR1.

Malondialdehyde-Acetaldehyde Modified (MAA) Proteins Differentially Effect the Inflammatory Response in Macrophage, Endothelial Cells and Animal Models of Cardiovascular Disease.

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. Currently, the mechanism(s) by which inflammation contributes to this disease are not entirely understood. Inflammation is known to induce oxidative stress, which can lead to lipid peroxidation. Lipid peroxidation can result in the production of reactive by-products that can oxidatively modify macromolecules including DNA, proteins, and lipoproteins. A major reactive by-product of lipid peroxidation is malondialdehyde (MDA). MDA can subsequently break down to form acetaldehyde (AA). These two aldehydes can covalently interact with the epsilon (ε)-amino group of lysines within proteins and lipoproteins leading to the formation of extremely stable, highly immunogenic malondialdehyde/acetaldehyde adducts (MAA-adducts). The aim of this study was to investigate the inflammatory response to MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). We found that animals injected with LDL-MAA generate antibodies specific to MAA-adducts. The level of anti-MAA antibodies were further increased in an animal model of atherosclerosis fed a Western diet. An animal model that combined both high fat diet and immunization of MAA-modified protein resulted in a dramatic increase in antibodies to MAA-adducts and vascular fat accumulation compared with controls. In vitro exposure of endothelial cells and macrophages to MAA-modified proteins resulted in increased fat accumulation as well as increased expression of adhesion molecules and pro-inflammatory cytokines. The expression of cytokines varied between the different cell lines and was unique to the individual modified proteins. The results of these studies demonstrate that different MAA-modified proteins elicit unique responses in different cell types. Additionally, the presence of MAA-modified proteins appears to modulate cellular metabolism leading to increased accumulation of triglycerides and further progression of the inflammatory response.

Improvement on the extraction efficiency of low density lipoprotein in an ionic liquid microemulsion

A novel microemulsion is developed at room temperature with 30 µL of sodium alginate sulfate (SAS, 0.02 mol/L), 0.005 g bis (2-ethylhexyl) succinate sulfonate (AOT) and 270 µL of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) ionic liquid as aqueous phase, surfactant and IL phase, respectively. The SAS/AOT/BmimPF6 microemulsion significantly improves the extraction efficiency for low density lipoprotein (LDL). 96% LDL in a 300 µL of PBS is selectively extracted into a same volume of microemulsion, with respect to those of 67%, 76% and 85% by BmimPF6, H2O/AOT/BmimPF6 microemulsion and sodium alginate (SA)/AOT/BmimPF6 microemulsion. LDL in the SAS/AOT/BmimPF6 microemulsion is distributed both in BmimPF6 via hydrophobic interaction and in the “pools” of the microemulsion via electrostatic interaction with AOT and specific interaction between LDL with SAS. 83% of LDL in the microemulsion can be readily back extracted into an aqueous phase with 0.8% (m/v) of sodium dodecyl sulfate (SDS) as stripping reagent. For practical applications, LDL in human serum is selectively extracted with the microemulsion, as demonstrated by enzyme linked immunosorbent assay (ELISA) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Temperature Influence on Myocardial Cell Cytotoxicity of the Extracellular Photosensitization Reaction with Talaporfin Sodium and Serum Proteins at 17°-37°C.

We investigated the binding of talaporfin sodium with albumin and its photocytotoxicity during temperature changes by measuring absorbance spectra. The targeted tissue temperature differs according to the procedure. The photocytotoxicity efficiency should be investigated quantitatively because efficiency changes arising from temperature changes are expected. The temperature dependence of talaporfin sodium binding with human serum albumin (0-20 mg/mL), high-density lipoprotein (0-0.04 mg/mL), and low-density lipoprotein (0-0.14 mg/mL) was investigated at 17°C, 27°C, and 37°C by measurement of absorbance spectra. Cell lethality was measured using a water-soluble tetrazolium-8 assay at 2 h after the photosensitization reaction at 17°C and 37°C. The binding ratios of talaporfin sodium with high-density lipoprotein decreased by 6.3% and those with low-density lipoprotein decreased by 12.8% when the temperature increased from 17°C to 37°C. Cell lethality increased significantly with a temperature rise from 17°C to 37°C at irradiation exposure of 20 and 40 J/cm2 and talaporfin sodium concentration of 20 μg/mL. From our in vitro data, we can predict that the change in photocytotoxicity efficiency would be negligible with a temperature decrease of <5°C from the body temperature in the case of photodynamic ablation with a short drug-light interval.

Fluorination of phthalocyanine substituents: Improved photoproperties and enhanced photodynamic efficacy after optimal micellar formulations

A fluorinated phthalocyanine and its non-fluorinated analogue were selected to evaluate the potential enhancement of fluorination on photophysical, photochemical and redox properties as well as on biological activity in cellular and animal models. Due to the pharmacological relevance, the affinity of these phthalocyanines towards biological membranes (logPow) as well as their primary interaction with human serum albumin (HSA) or low-density lipoprotein (LDL) were determined. Water-dispersible drug formulation of phthalocyanines via Pluronic®-based triblock copolymer micelles was prepared to avoid self-aggregation effects and to improve their delivery. The obtained results demonstrate that phthalocyanines incorporation into tunable-polymeric micelles significantly enhanced their cellular uptake and their photocytotoxicity. The improved biodistribution and photodynamic efficacy of the phthalocyanines-triblock copolymer conjugates was also confirmed in vivo in CT26 bearing BALB/c mice. PDT with both compounds led to tumor growth inhibition in all treated animals. Fluorinated phthalocyanine 2 turned out to be the most effective anticancer agent as the tumors of 20% of mice treated regressed completely and did not appear for over one year after treatment.

Modified (desialylated) low-density lipoprotein measured in serum by lectin-sorbent assay

Modified low-density lipoprotein (LDL) with a low sialic acid content was found in the blood of patients with coronary atherosclerosis. This desialylated lipoprotein causes lipid accumulation in arterial smooth-muscle cells and stimulates cell proliferation and production of the extracellular matrix, i.e., induces all atherogenic manifestations at the cellular level. We have developed a lectin-sorbent assay for the determination of desialylated LDL in sera. The assay is based on the binding of desialylated LDL by immobilized Ricinus communis agglutinin with subsequent measurement of lipoprotein through use of anti-apolipoprotein (apo) B antibody. The assay is sensitive to desialylated apo B concentrations as low as 5 micrograms/L. Comparison between the lectin-sorbent assay and a lectin chromatographic technique showed a good correlation. This determination of modified desialylated LDL in human serum with high accuracy and reproducibility may help establish the diagnostic value of this lipoprotein as a risk factor of atherosclerosis.

Fluorescent nanodiamond as a probe for the intercellular transport of proteins in vivo

This study investigates the intercellular transport of yolk lipoproteins in Caenorhabditis elegans by using fluorescence lifetime imaging microscopy (FLIM) and fluorescent nanodiamonds (FNDs) as photostable labels and tracers. The yolk lipoproteins in the nematode are similar to human serum low-density lipoproteins (LDLs), serving as an intercellular transporter of fat molecules and cholesterol. To study this fundamentally important process, FNDs were first coated with yolk lipoprotein complexes (YLCs) and then microinjected into the intestinal cells of the living organism. Real-time imaging over a time period of more than 50 min with FLIM revealed the process of YLC-FND secretion from the intestine to the pseudocoelomic space, followed by transporting into oocytes and subsequent accumulation in the multi-cellular embryos derived from the oocytes. Colocalization studies of the rme-2 adult hermaphrodites expressing green fluorescent protein (GFP)-tagged YLCs confirmed that the injected YLC-FNDs were taken up by oocytes through endocytosis mediated by the LDL receptor, RME-2, functioning as an YLC receptor. Our results demonstrate that FND is useful as a biomolecular nanocarrier without significantly altering the functionality of the cargos for intercellular transport, cell-specific targeting, and long-term imaging applications in vivo.

In vitro binding of human serum low-density lipoproteins by sulfated pectin derivatives

It was shown that sulfated pectin derivatives bind human serum low-density lipoproteins (LDLs) in vitro to a greater extent than native pectins. At the same time, the number of sulfate groups and the molecular weight of sulfated derivatives were crucial factors. The sulfated pectin derivatives with molecular weights more than 200 kDa containing 45 wt % sulfate groups had the greatest ability to bind LDLs, while the sulfated derivatives with molecular weights lower than 50 kDa containing 5% sulfate groups exhibited the lowest activity.

Phosphoethanolamine-complexed C-reactive protein: A pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum

Background C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL. Methods We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation. Results We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum. Conclusions The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.

Generation and characterization of IgG monoclonal antibodies specific for malondialdehyde.

Numerous studies have indicated that the oxidative modification of low-density lipoprotein (LDL) plays a critical role in the pathogenesis of atherosclerosis. Malondialdehyde-modified LDL (MDA-LDL) is one of the candidate oxidative products. Therefore, to allow the assessment of oxidized LDL in human serum, we developed monoclonal antibodies for MDA-LDL. Two of these-MDA1 and MDA2-bound to oxidized LDL but not to native LDL by Western blot analysis. The murine monoclonal antibodies to oxidized LDL have potential clinical implications, as imaging agents, for defining the compositions of atherosclerotic vessels in vivo.

Comparative analysis of foetal calf and human low density lipoprotein: relevance for pharmacodynamics of photosensitizers

The effects of differences in lipoprotein content on the distribution of the novel hydrophobic photosensitizer n-butyl-3-[18-(2-butylcarbamoyl-ethyl)-3,7,12,17-tetramethyl-18,13-divinyl-22,24-dihydro-porphin-2-yl]propionamide (PP-N-3) and haematoporphyrin ester (HpE), a relatively hydrophilic photosensitizer, in human (HS) and foetal calf sera (FCS), were investigated. The binding characteristics of human and foetal calf low-density lipoprotein (LDL) were characterised using a human fibroblast line (Vag 12). The uptake into cells of HpE and PP-N-3 was also examined. A comparison of the lipoprotein content, composition and receptor-binding characteristics of foetal calf and human serum was also carried out. LDL content was measured directly using sequential ultracentrifugation to isolate LDL. In our study, we found haematoporphyrin ester to bind to human very low-density lipoprotein (VLDL), LDL and high-density lipoprotein (HDL) in the ratio 2:31:65. In the case of PP-N-3 this ratio was 56:10:33. As VLDL was not detected in foetal calf serum, only binding to LDL and HDL was observed. Using the sequential ultracentrifugation technique, foetal calf serum was found to contain LDL which in turn did bind to human LDL receptors. The uptake of PP-N-3 and HpE in the presence of low density lipoprotein from foetal calf serum (FC-LDL) was not significantly different to values observed in the presence of human serum low density lipoprotein (HS-LDL).

Identification of oxidized low-density lipoprotein in human serum by NMR spectroscopy

1. In this study we compared the 500 MHz 1H-NMRs from native and oxidized low-density lipoproteins. 2. The measurements revealed a characteristic pattern of three resonances in spectra from oxidized, but not from native low-density lipoprotein at 1.17 p.p.m., 1.18 p.p.m. and 1.20 p.p.m. (relative to 3-trimethylsilyl-[2,2,3, 3-2H4]-propionate).3.A quantitative comparison between these resonances in sera from patients with coronary heart disease and healthy control subjects revealed that the intensity was significantly higher in patients with coronary heart disease (1.17 p.p.m.: 0.026+/-0.014 versus 0.015+/-0.019; 1.18 p.p.m.: 0.032+/-0.011 versus 0.017+/-0.021; 1.20 p.p.m.: 0.030+/-0.066 versus 0.010+/-0.005; P<0.05 compared with healthy control subjects for each resonance).4.Fractionation of sera from patients with coronary heart disease revealed that the resonances equal to those obtained from experimentally oxidized low-density lipoprotein are indeed caused by the low-density lipoprotein fraction of the sera.5. When the NMRs from sera were calibrated with oxidized low-density lipoprotein prepared by Cu2+ oxidation, a concentration of 66.5+/-28.6 microgram/ml and 36.3+/-23.7 microgram/ml (P<0.05) was estimated in patients with coronary heart disease and healthy subjects respectively. Elevated levels of oxidized low-density lipoprotein also occurred in those patients with normal serum concentrations of total low-density lipoprotein.6. The study shows a simple method to measure oxidized low-density lipoprotein in human serum and may gain interest to assess the cardiovascular risk factor profiles more completely.

Identification of oxidized low-density lipoprotein in human serum by NMR spectroscopy

Identification of oxidized low-density lipoprotein in human serum by NMR spectroscopy

Aggregation of dimyristoylphosphatidylglycerol liposomes by human plasma low density lipoprotein

Turbidity (absorbance at 470 nm) measurements revealed human serum low density lipoprotein (LDL) to cause, within a few minutes and at physiological pH and [NaCl], the aggregation of liquid crystalline large unilamellar liposomes (LUVs) of dimyristoylphosphatidylglycerol (DMPG). No evidence for concomitant lipid or aqueous contents mixing was obtained with fluorescent assays for these processes, in keeping with the lack of fusion of LUVs. Involvement of apoB is implicated by the finding that tryptic digestion of LDL abrogates its ability to cause aggregation. Aggregation is not caused by VLDL, HDL2, or HDL3. Interestingly, also oxidised LDL failed to aggregate DMPG vesicles. Aggregation of DMPG LUVs by LDL did depend on the ionic strength of the medium as well as on the phase state of the lipid. More specifically, below the main transition temperature Tm maximal aggregation was seen in the presence of 25–100 mM NaCl, whereas slightly higher (up to 150 mM) [NaCl] were required when T>Tm. Aggregation due to LDL was also observed for dimyristoylphosphatidylserine as well as for dipalmitoylphosphatidylglycerol LUVs, whereas liposomes composed of either unsaturated acidic phospholipids or different phosphatidylcholines were not aggregated. Involvement of electrostatic attraction between the acidic phosphate of DMPG and cationic residues in apoB is suggested by the finding that increasing the content of dimyristoylphosphatidylcholine (DMPC) in DMPG liposomes reduced their aggregation and at XDMPC=0.50 no response was evident. Notably, increasing the mole fraction of 1-palmitoyl-2-oleyl-PG (POPG) in DMPG LUVs progressively reduced their aggregation by LDL and at XPOPG=0.50 there was complete inhibition. The latter effect of POPG is likely to be due to augmented hydration of the unsaturated lipid constituting a barrier for the contact between apoB and the vesicle surface. In keeping with this view, the presence of the strongly hygroscopic polymer, poly(ethylene glycol) at 1% (by weight) enhanced the aggregation and could partly reverse the inhibition by POPG.

Microenvironment effects on the excited state properties of psoralens: a clue to their photobiological activity.

The singlet and triplet excited state parameters (phi f, tau t and phi T) of psoralen (PSO) and derivatives 4,6,4'-trimethylangelicin (TMA) and 4,5',8-trimethylpsoralen (TMP) show an extreme sensitivity to solvation in dioxane/water mixtures. These effects are attributed to the variation of the S1-->S0 internal conversion rate constant kic, which is the nonradiative deactivation path dominating their photophysical behavior. Depending on the compound, kic is very high, (approximately 1 x 10(10) s-1) in nonpolar solvents and then decreases to a low value (3 x 10(8) s-1), with increasing solvent polarity. This work shows that dioxane/water mixtures display the same solvent-induced changes in the electronic structure of psoralens during solvation as those induced by the biological microenvironment sensed by the drug's localization. This mixture matches the photophysical parameters of psoralens observed in protic and aprotic pure solvents, in micelles, in liposomes and in human serum low-density lipoproteins (LDL). They can be used to probe the solvating ability of the interaction site in macrocyclic hosts. A particular localization site, i.e. the more (TMA and TMP) or less (PSO) lipophilic sites found when in interaction with LDL, determines the amount of the triplet reactive state of psoralens and the molecular mechanism available for photoreaction: oxic (type I and type II) or anoxic (type III) pathways.

Modified (desialylated) low-density lipoprotein measured in serum by lectin-sorbent assay

Modified low-density lipoprotein (LDL) with a low sialic acid content was found in the blood of patients with coronary atherosclerosis. This desialylated lipoprotein causes lipid accumulation in arterial smooth-muscle cells and stimulates cell proliferation and production of the extracellular matrix, i.e., induces all atherogenic manifestations at the cellular level. We have developed a lectin-sorbent assay for the determination of desialylated LDL in sera. The assay is based on the binding of desialylated LDL by immobilized Ricinus communis agglutinin with subsequent measurement of lipoprotein through use of anti-apolipoprotein (apo) B antibody. The assay is sensitive to desialylated apo B concentrations as low as 5 micrograms/L. The intraassay and interassay CVs were 4.8% and 11.3%, respectively. Comparison between the lectin-sorbent assay and a lectin chromatographic technique showed a good correlation. This determination of modified desialylated LDL in human serum with high accuracy and reproducibility may help establish the diagnostic value of this lipoprotein as a risk factor of atherosclerosis.

The effects of hyperthermia on human endothelial monolayers: modulation of thrombotic potential and permeability.

The effects of hyperthermia on potentially prothrombotic endothelial function were investigated by measuring levels of von Willebrand factor, thrombospondin, tissue plasminogen activator and plasminogen activator inhibitor-1 secreted by unstimulated human umbilical vein endothelial cells cultured at 37 degrees C, 39 degrees C, 41 degrees C and 43 degrees C for 24 h. Endothelial barrier function at 43 degrees C was compared with that at 37 degrees C by measuring permeability to radiolabelled human serum albumin and low density lipoprotein. Thrombospondin levels were unaffected by a temperature of 39 degrees C; they increased after 3 h at 41 degrees C and subsequently declined to values significantly below the 37 degrees C control. At 43 degrees C, secretion exhibited a time-dependent decrease. Secretion of von Willebrand factor was not discernibly affected by exposure to 39 degrees C or 41 degrees C. Its response to 43 degrees C resembled that of thrombospondin to 41 degrees C. In contrast, elevated temperatures markedly increased plasminogen activator inhibitor-1 while decreasing t-PA secretion, though after prolonged exposure to 43 degrees C the levels of both returned to control values. After 12-24 h at 43 degrees C, endothelial permeability to both albumin and low density lipoprotein increased markedly. Vascular endothelium may contribute to the thrombotic tendency associated with heat stroke by increasing access to the prothrombotic subendothelium and reducing fibrinolysis.

Thermodynamics of the binding of hematoporphyrin ester, a hematoporphyrin derivative-like photosensitizer, and its components to human serum albumin, human high-density lipoprotein and human low-density lipoprotein.

The phenomena of the high affinity of porphyrins to the human serum proteins, albumin, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) is well established. Yet, evaluation of the activities of these proteins as endogenous porphyrin carriers, especially with respect to receptor-mediated porphyrin uptake into tumor cells, the merits of which are still in dispute, requires more quantitative protein-porphyrin binding data. As a continuation of previous studies on this issue, the binding of several porphyrin systems to each of the three proteins, employing previously developed spectral methodologies, was studied. The specific systems reported here are hematoporphyrin ester (HPE), which is a novel hematoporphyrin derivative (HPD)-like system, two porphyrin trimers (denoted O1 and O2) and a porphyrin dimer (denoted O3) isolated from HPE. Human serum albumin (HSA) was found to have a single high-affinity site for the monomeric components of HPE, with an equilibrium binding constant of 3.6 x 10(6). The equilibrium parameters determined for the binding of the three HPE-isolated oligomers to each of the serum proteins are: (1) Binding constants (Kb') of 2.3 x 10(6), 6.9 x 10(4) and 1.5 x 10(4) and number of sites per protein molecule (n) of 3, 1 and 5, for the binding of O1, O2 and O3, respectively, to HSA. (2) Kb' values of 15.5 x 10(3), 15.3 x 10(3) and 6.6 x 10(3) and n values of 1, 2 and 2, for the binding of O1, O2 and O3, respectively, to HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of low-density lipoproteins with gangliosides

The ganglioside uptake capacity of human serum low-density lipoproteins (LDL), the mode of ganglioside-LDL binding, and the influence of gangliosides on the floatation properties, size distribution, stability and fluorescence of LDL were investigated. The data obtained suggest that both hydrophobic and electrostatic forces are involved in formation of ganglioside-LDL complexes, but the former appear to be more important. Although association of gangliosides with LDL is predominantly unspecific, nonsaturable, and weak, a small saturable component due to specific ganglioside-apolipoprotein binding, also appears to be involved. In the presence of gangliosides the lipoprotein particles aggregate, the intrinsic fluorescence of LDL and their interaction with antibodies against apo-B change indicating that the state of apo-B [corrected] is modified by gangliosides.

Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis

An electron spin probe study was made of the effect of lipid peroxidation (LPO) on the structure of surface proteolipid layer of human serum low-density lipoproteins (LDL). The results obtained with a positively charged spin label and stearic acid spin probes with doxyl labels at positions 5, 12, and 16 revelaed that LPO caused a decreased in phospholipid molecule mobility both in the region of polar heads and in the region of acyl chains till the depth of a least 1.7 mm from water-lipid interface. Under relatively high levels of oxidation (more than 6 μmol MDA/g LDL phospholipid) the polarity of lipid phase increased. The decrease in efficiency of tryptophan fluorescence quenching by nitroxide fragments incoporated in hydrophobic regions at the depth of ∼2 nm from water-lipid interface indicated that lipid-protein interaction was disturbed as a result of oxidation of LDL lipids. In addition, the LPO-induced modification of apo-B, the main protein of LDL, was examined with maleimide spin label. LPO led to increase in mobility of strongly immobilized maleimide labels and in the number of weakly immobilized ones. Oxidized LDL revealed decreased ability to incorporate spin-labeled steroid (androstane) as compared to antive ones. LPO-induced structural changes of LDL surface are supposed to be a reason of enhanced accumulation of cholesterol in human monocytes during their incubation with oxidized LDL. The cholesterol content in red cells was shown to be directly correlated to MDA content in apo-B containing lipoproteins but not in whole serum. Our findings suggest that free radical modification of serum lipoproteins but not solely an increased level of LPO products in blood is one important cause for cholesterol accumulation in cells and, apparently, for their transformation into foam cells during atherosclerosis.