Lipid composition of multiple modified (desialylated) low-density lipoproteins

It is shown that the lipid composition of desialylated low-density lipoproteins differs considerably from that of native (sialylated) lipoproteins. Desialylated lipoproteins have a lower content of fat-soluble vitamins and a higherin vitro oxidizability. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 37–39, July, 1996     

Chemiluminescence study of the contents of the products of Cu2+-induced lipid peroxidation in different fractions of human blood lipoproteins

It is demonstrated that the content of the primary products of lipid peroxidation reaches the maximum after about 1-h incubation with Cu²⁺ and then declines. At a Cu²⁺ concentration of about 10–15 μM, the content of lipid peroxidation products is maximal; it does not rise with a further increase in the Cu²⁺ concentration. Comparison of the kinetics of lipid peroxidation in different lipoprotein fractions shows that low density lipoproteins are much more strongly oxidized than high density lipoproteins. A strong positive correlation between the amplitude of the chemiluminescence burst and the diene conjugate content is established in 79 independent measurements. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 144–148, February, 1995     

In vivo intensification of free-radical oxidation of low-density lipoproteins in the plasma of patients with coronary heart disease treated with β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor pravastatin and inhibition of lipid peroxidation with ubiquinone Q10

Pravastatin, an inhibitor of β-hydroxy-β-methylglutaryl coenzyme A reductase, the key enzyme of cholesterol biosynthesis,in vivo elevated the content of primary and secondary products of free-radical oxidation in low-density lipoproteins in patients with coronary heart disease, while combined treatment with pravastatin and ubiquinone Q₁₀ sharply decreased this parameter. Ubiquinone Q₁₀ prevented pravastatin-induced inhibition of antioxidant enzymes superoxide dismutase and lipid peroxidase utilizing reactive oxygen species in the blood. These data indicate that ubiquinone Q₁₀ would be appropriate for use in combination with statins, inhibitors of β-hydroxy-β-methylglutaryl coenzyme A reductase, for the therapy of patients with coronary heart disease. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 176–179, February, 2000     

Interaction of low-density lipoproteins and elastins from the intima and media of human intact and atherosclerotic aorta

Binding of low-density lipoproteins to elastins from the media and proteoglycan and muscle sublayers of human intact and atherosclerotic aorta was studied. Circulating modified lowdensity lipoproteins intensively bound to elastin due to the loss of sialic acid. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 180–182, February, 2000     

Endothelial cells induce oxidation of low-density lipoproteins

The ability of human umbilical vein endothelial cells to oxidize low-density lipoproteins during a 24-h incubation was assessed from the accumulation of products reacting with 2-thiobarbituric acid and fluorescent products in the incubation medium. It depends on the concentration of lipoproteins and the incubation conditions and increases in the following series: aerobic conditions<ischemia<ischemia+reperfusion. This indicates that ischemia and reperfusion of vascular endothelium may promote parietal oxidation of lowdensity lipoproteins and selective atherosclerotic damage to the vascular wall. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 314–317, September, 1998     

Cytotoxic effect of low-density lipoproteins on intact, ischemic, and reperfused endothelial cells

The cytotoxic effect of low-density lipoproteins on cultured human umbilical vein endothelial cells increases with their concentration, degree of oxidation, and incubation time, being more pronounced in ischemia or ischemia+reperfusion than in aerobic conditions. Synergism of the cytotoxic effect of lipoproteins with the damaging effect of ischemia and reperfusion promotes the development of atherosclerotic lesions of the vascular wall at sites predisposed to the damage by the ischemia/reperfusion. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 302–306, September, 1998     

Inhibition of low density lipoprotein oxidation by melatonin

The antioxidant activity of the lipophilic hormone melatonin, “an ideal inhibitor of free radicals,” is studied in models of cellular (peritoneal mouse macrophages) and copper-induced oxidation of low density lipoproteins. Oxidative modification of low density lipoproteins is assessed by accumulation of thiobarbituric acid reactive substances and degradation of¹²⁵I-labeled lipoproteins in a fresh culture of macrophages. Melatonin inhibits in a dose-dependent manner cellular and copper-induced oxidation of lipoproteins and production of the superoxide anion radical by macrophages, the mean concentrations of 50% inhibition being 300, 1230, and 900 μM, respectively. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 399–402, October, 1996     

Effects of low-density lipoproteins on blood coagulation and fibrinolytic activity

In vitro experiments showed that copper-oxidized low-density lipoproteins activate factors of the prothrombin complex in the whole blood and inhibit fibrin generation in both blood and plasma. Moreover, oxidized low-density lipoproteins inhibit fibrinolysis and impair the structure of fibrin clot, which results in hypercoagulation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp. 637–639, June, 2000     

Effect of naftidrofuryl on lipid peroxidation in serum and erythrocyte plasma membrane of patients with diabetes mellitus

Effect of naftidrofuryl, a blocker of serotonin 5S₂-receptors (Dusodril-retard), on the malonic dialdehyde content in the serum and erythrocyte membranes is studied in diabetics with and without angiopathies. A 40-day treatment with Dusodril-retard normalizes the serum content of malonic dialdehyde, an intermediate product of lipid peroxidation, and has no effect on the malonic dialdehyde content of the erythrocyte plasma membrane. A negative correlation is established between blood levels of total cholesterol, β lipoproteins, and malonic dialdehyde levels in patients with diabetes mellitus. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 9, pp. 338–341, September, 1996     

An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women

Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum. Received: 14 May 2002 / Accepted: 27 November 2002 Correspondence to ü. Mutlu-Türkoğlu     

Trimetazidine as indirect antioxidant

One-month therapy with trimetazidine sharply decreased the content of free radical oxidation products, lipid peroxides and malonic dialdehyde, in atherogenic low-density lipoproteins in patients with coronary heart disease. Activity of glutathione peroxidase utilizing lipid peroxides in the plasma markedly increased during trimetazidine therapy. The data suggest that trimetazidine not directly interacting with free radicals attenuates the adverse effects of intensive free radical oxidation in coronary heart disease. This effect is mediated via activation of antioxidant enzymes, which diminishes negative consequences of ischemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 395–398, October, 2000     

Cerivastatin modulates antiatherogenic properties of high-density lipoproteins in patients with coronary heart disease and hyperlipidemia

The effects of cerivastatin on antiatherogenic properties of high-density lipoproteins were studied in patients with coronary heart disease and hyperlipidemia. Apart from hypolipidemic effects, cerivastatin changed the phospholipid composition of high-density lipoproteins and improved their cholesterol-acceptor properties. This effect was most pronounced in the serum from patients with low content of high-density lipoprotein cholesterol. These data indicate that cerivastatin modulates antiatherogenic properties of high-density lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 433–436, October, 2000     

Effects of native and oxidized low-density lipoproteins on macrophage chemiluminescence

Effects of low-density lipoproteins (LDL) obtained from healthy donors and patients with hypercholesterolemia on spontaneous luminol-dependent and zymosan-induced chemiluminescence of rat macrophages were studied. Unlike LDL from healthy donors, native LDL from patients with hypercholesterolemia inhibited spontaneous chemiluminescence of macrophages. Simultaneous incubation with endotheliocytes from the umbilical vein led to the appearance of inhibitory effect of LDL from healthy donors (incubation for 24 h) and potentiated this effect of LDL from patients with hypercholesterolemia (incubation for 6 and 24 h). The inhibitory effect was more pronounced in LDL incubated with umbilical endotheliocytes under ischemic conditions then after aerobic incubations. This corresponded to higher oxidation of LDL confirmed by accumulation of thiobarbituric acid-reactive substances, increased fluorescence, and high electrophoretic mobility in agarose gel. These data suggest that the model system of spontaneous and zymosan-induced chemiluminescence of macrophages can be used for evaluating the degree of oxidation and potential atherogenicity of LDL. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 514–517, November, 1999     

Inhibition of human plasma ApoB-lipoproteins

The effects of astaxanthine and β-carotene on the oxidation of isolated human plasma apoB-lipoproteins induced by copper ions or hemin/hydrogen peroxide are studied. Astaxanthine inhibits the formation of both primary (diene conjugates) and secondary (thiobarbituric acid-reactive substances) products of lipid perioxidation. Antioxidant activity of astaxanthine is observed in the concentration range 20–100 μg/mg protein of apoB-lipoproteins. The antioxidant activity of astaxanthine is higher than that of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 285–288, March, 1997     

Characterization of specific binding sites for high-density lipoproteins on rat hepatocytes: Effects of estradiol and testosterone

Two types of binding sites for high-density lipoproteins (HDL): P₁ and P₂ K_dl=20 and K_d2=2.5μg/ml, N₁=130 and N₂=35 ng/mg cell protein) are identified on the surface of rat hepatocytes. Conditions for predominant determination of P₂ are created by employing radiolabeled lipoproteins (¹²⁵I-HDL) with a high specific activity (1000 dpm) and the differences in the kinetics of the P₁-and P₂-¹²⁵I-HDL complex formation. P₂ predominate on hepatocytes from females. The addition of estradiol to a culture of hepatocytes from males increases the content of P₂, while the addition of testosterone to hepatocytes from females decreases the content of P₂ to the levels determined in males. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 629–634, December, 1996     

Antioxidant probucol as an effective scavenger of lipid radicals in low density lipoproteinsin vivo andin vitro

Probucol in concentrations of 10–15 μM effectively inhibits Cu²⁺-induced free radical oxidation of native low density lipoproteins and in concentration of 100 μM it inhibits lipoperoxide formation. The mean plasma concentration of probucol in patients receiving 250 mg of this drug is 25 μM. Both 250 and 1000 mg probucol daily during 3–6 month block the oxidation of isolated low density lipoproteins. Electron paramagnetic resonance spectrometry data showed that probucol incorporatedin vivo into lipoprotein particles interacts with lipid radicals yielding long-lived phenoxyradicals. Probucol can be used in complex therapy of atherosclerosis as an antioxidant drug and its dose required for lipoprotein protection against atherogenic modification can be decreased to 250 mg/day. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 186–189, August, 1999     

Multiple modifications of low-density lipoproteins in the blood of patients with atherosclerosis

Atherogenic low-density proteins (LDL) found in human blood — desialylated, electronegative, and small dense LDL — share many chemical and physical characteristics and appear to represent the same subfraction of multiply modified lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 118–121, August, 1995 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

Protein-bound lipids in human low density lipoproteins

In vitro oxidation of low density lipoproteins is found to be accompanied by accumulation of sterol and phospholipid residues covalently bound with apolipoprotein B. The content of protein-bound lipids in the subfraction of desialylated low density lipoproteins from healthy subjects and patients with coronary atherosclerosis is shown to be higher than that in native lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, No. 8, pp. 155–157, August, 1995 Presented by E. I. Chazov, Member of the Russian Academy of Medical Sciences     

Multiply modified desialylated low-density lipoproteins: Physicochemical properties

Sialylated and desialylated low-density lipoproteins from human blood are shown to differ markedly in physicochemical parameters. The latter lipoproteins have a smaller particle size, are denser and more electronegative, and tend to aggregate more readily than the former. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 42–43, January, 1996 Presented by E. I. Chazov, Member of the Russian Academy of Sciences     

Immunochemical analysis of common antigenic determinants in insulin and apoprotein B Molecules

A study is performed of the mechanism underlying stress diabetes, which develops in human beings and animals under stress. Dot-immunoanalysis shows the presence of common antigenic determinants in insulin, apoprotein B, and apoprotein B-containing low density and very low density lipoproteins isolated from human and rat serum. Electrophoresis, immunoelectroblotting, and immunoenzyme analysis reveal 5–6 peptides belonging to apoB, which specifically react with anti-insulin and anti-very low density lipoprotein antibodies. Insulinlike immunoreactivity is also identified in human serum supernatant obtained after precipitation of the total low density and very low density lipoprotein fraction and after removal all lipoproteins from it. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 258–261, September, 1994