A Sorbent with Synthetic Ligand for Removing Pro-atherogenic and Pro-inflammatory Components from Human Blood Plasma.

Elevated levels of apoB-100 containing lipoproteins and markers of systemic inflammation are often observed in patients with cardiovascular diseases. The concentrations can be reduced by pharmacotherapy or extracorporeal treatment. The sorbent, which removes CRP and atherogenic lipoproteins, simultaneously reduces the bloodstream concentration of these components. The efficacy and selectivity of the designed sorbent were studied, desorption constants of CRP (Kd = 4.2 × 10-8 M) and LDL (Kd = 7.7 × 10-7 M) were distribution coefficients of CRP (Kc = 101) and Lp(a) (Kc = 38) were calculated, and the ability to bind large amounts of atherogenic lipoproteins (up to 32 mg of TC per mL of the sorbent gel) was demonstrated. Our sorbent can be recommended for performing complex removal of CRP and atherogenic lipoproteins from the blood plasma in patients with refractory hyperlipidemia and CVD that are accompanied by elevated levels of CRP.

A Low-Molecular-Weight Phenotype of Apolipoprotein(a) as a Factor Provoking Accumulation of Cholesterol by THP-1 Monocyte-Like Cells.

Increased concentration of lipoprotein(a) is a risk factor of coronary heart disease. lipoprotein(a) consists of LDL-like and highly polymorphic apolipoprotein(a). Here we studied the effect of lipoprotein(a)-containing sera with different apolipoprotein(a) phenotypes on lipid accumulation by THP-1 monocyte-like cells. Cholesterol concentration in lysates of THP-1 cells was significantly higher after their incubation with lipoprotein(a)-containing serum samples with low-molecular-weight phenotype of apolipoprotein(a) in comparison with samples with a high-molecular-weight apolipoprotein(a) phenotype irrespective of initial cholesterol level as well as serum concentrations of apoB-100, oxidized LDL, and circulating immune complexes. The presence of the most atherogenic small dense LDL subfractions in examined sera in addition to a low-molecular-weight apolipoprotein(a) phenotype resulted in significant elevation of cholesterol accumulation by THP-1 cells. The data obtained explain greater atherogenicity of lipoprotein(a) with low-molecular-weight apolipoprotein(a) phenotype.

[The effect of increased concentration of lipoprotein (a) on identification of sub-faction of lipoproteins using native electrophoresis technique].

The quantitative analysis of sub-fractions of lipoproteins acquires growing significance in diagnostic and prognosis of cardiovascular diseases. It is well known that presence of lipoprotein (a) in high concentrations significantly distorts results of biochemical analysis, in particular detection of level of cholesterol of low-density lipoproteins. The lipoprotein (a) is a heterogeneous particle and its mobility in the systems used for analysis of sub-fractions of lipoproteins can have significant variability that will bring inaccuracy into results. The data concerning relationship between lipoprotein (a) and sub-fractions of lipoproteins and also their differentiation in various systems of determination of lipid spectrum are quite numerous. The given study is considered as actual one because it analyses input of lipoprotein (a) into results of detection of sub-fractions using the technique with diagnostic significance. The study was carried out for evaluating possible input of lipoprotein (a) into results of quantitative estimation of sub-fractions of lipoproteins by technique of native electrophoresis in polyacrylamide gel used for diagnostic of cardio-vascular diseases. To detect concentration of lipoprotein (a) in blood serum the technique of enzyme-linked immunosorbent assay was applied. The qualitative valuation of content of sub-fractions of lipoproteins was implemented using system Lipoprint Quantimetrix (USA). The sub-fractions of lipoproteins were detected in samples of serum of healthy donor and normolipidic patients before and after removal of lipoprotein (a) using technique of affine chromatography in vitro. It turned out that after removal of lipoprotein (a) analysis of sub-fractions of lipoproteins in plasma of healthy donor detects significant decreasing of level of lipoproteins of medium density. The samples of serum of patients with atherosclerosis besides removal of sub-fractions of lipoproteins of medium density, decreasing of level of large sub-fractions of low density lipoproteins was observed. The analysis of samples obtained after procedures of therapeutic lipoprotein (a) apheresis using columns "Lp (a) Lipopak" (Russia) demonstrated that along with removal of lipoprotein (a), decreasing of concentration of sub-fraction C lipoproteins of medium density in all samples that substantiates in vitro data. In patients without affection and with multi-vessel lesion of coronary bloodstream reliable differences in concentration of lipoproteins of medium density were established. The received data testify that high level of lipoprotein (a) can contribute significant inaccuracies into results of detection of subfractions of lipoproteins. Therefore, application of system Lipoprint (Quantimetrix USA) provides no opportunity to unequivocally interpret data concerning input of sub-fractions of lipoproteins into risk of development of cardio-vascular diseases in patients with pathological lipid profile and higher concentration of lipoprotein (a).

[Elevated Lipoprotein(a) Cncentration and Presence of Subfractions of Small Dense Low Density Lipoproteins as Independent Factors of Risk of Ischemic Heart Disease].

AIM: To study relation of lipoproteina - Lp(a) and subfractional composition of apoB containing lipoproteins to the presence of ischemic heart disease (IHD). Manerial and methods. Parameters of lipid spectrum, Lp(a), and subfractions of apoB containing lipoproteins were determined in blood serum of 187 patients with known data of instrumental examination. RESULTS: Lp(a) concentration was not linked to any of risk factors, levels total cholesterol (TC), low and high density lipoprotein CH, and subfractions of lipoproteins. In total group triglyceride (TGG) level correlated with content of small dense LDL (sdLDL) (r=0.445, <0.0001) and mean dimension of LDL particles (r=-0.424, p<0.0001). This correlation was absent in the subgroup with Lp(a) more or equal 30 mg/dl and was strengthered among patients with normal Lp(a) level. In total group presence of IHD was associated with sex (r=0.325, p<0.0001), Lp(a) concentration (r=0.271, p=0.0001), and level of triglycerides (r=0.159, p=0.030). In multiple regression analysis levels of TG, Lp(a) and sdLDL were selected as factors independently associated with presence of IHD. Detection of subfractions sdLDL>2 mg/dl in blood plasma (atherogenic profile B), as well as lowering of concentration of large LDL subfractions significantly increased probability of IHD presence in patients with elevated Lp(a) concentration Lp(a) concentration. CONCLUSION: Lp(a) is an independent factor of risk of coronary atherosclerosis more significant than shifts in subfractional composition of apoB containing lipoproteins. In patients with Lp(a) concentration less or equal 30 mg/dl subfractions of sdLDL were directly related to TG. Level of sdLDL and large lipoproteins of intermediate density are directly related to the presence of IHD. Large LDL correlates with concentration of HDL DL C and probably is cardioprotective. sdLDL content>2 mg/l or hypertriglyceridemia (TG>1.7 mmol/l) significantly increase chances of detection of confirmed IHD in patients with elevated Lp(a).

[Effect of cascade plasma filtration on spectrum of subfractions of low density lipoproteins in blood plasma of patients with ischemic heart disease].

We studied effect of cascade plasma filtration on subfractions of low density lipoproteins (LDL) in 16 patients with ischemic heart disease (IHD) and hyperlipidemias refractory to drug therapy. The procedure caused 37.6 ± 1.4%, 43.1 ± 2.5%, and 50.9 ± 1.4% lowering of total, low density lipoprotein cholesterol, and apolipoprotein B-100, respectively. The use of filters led to removal of larger less atherogenic LDL-1 and LDL-2 subfractions with relative accumulation of small dense LDL-3, LDL-4, and LDL-5 subfractions. Lowering of concentrations of all LDL subfractions was caused by specific LDL apheresis by immunosorbtion in 4 patients with IHD. Removal of small dense LDL was more effective than that of large less atherogenic LDL-1 and LDL-2 subfraction. Thus we found differences in spectrum of LDL removed by cascade plasma filtration and immunosorbtion. The use of filters was associated with less effective removal of most atherogenic small dense LDL than of large LDL particles what led to redistribution of concentrations of various LDL subfractions towards atherogenic profile of lipoproteins. These results could constitute a basis for revision of methods of conduct of cascade plasma filtration procedures in patients with IHD.

[Soluble receptors for tumor necrosis factor and lipid metabolism as potential prognostic factors in patients with prostate cancer].

There was investigated the relationship of lipid metabolism, humoral immunity, high sensitivity C-reactive protein and soluble receptors for TNF-alpha with the presence, severity and prognosis of the disease in 85 patients with morphologically verified diagnosis of prostate cancer. Connection with the dynamics of change in PSA as a major predictor of the disease was observed for concentration sRI and sRII to TNF, PSA baseline, total cholesterol and LDL-cholesterol. During follow-up the relative risk of poor prognosis increased by 3 times, and death-in 8.7 times with increasing concentrations of soluble receptors for TNF. The concentration of soluble receptors for TNF may serve as an additional predictor of the presence and clinical course of disease in patients with prostate cancer.

[Effect of flavonoids of different structure on peroxidation of neutral lipids of animal origin].

The effect of flavonoids of different structure (baikalein, baikalin, quercetin, dihydroquercetin, genistein, and daidzein) on the process of formation of lipid hydroperoxides during thermoinduced autooxidation of neutral lipids of animal origin. The minimum inhibitory concentration of isoflavones was found to be equal to 10(-3) M. Effective inhibitory concentration of other flavonoids (except baikalin) was equal to 10(-4) M. Baikalin was an effective promoter of lipid peroxidation. The antioxidant activity of the flavonoids tested was calculated taking ionol as a reference.

[Effect of genistein and daidzein obtained by acid hydrolysis of their glycosides on phospholipid peroxidation]. / Vliianie na perekisnoe okislenie fosfolipidov genisteina i daidzeina, poluchennykh kislotnym gidrolizom ikh glikozidov.

A mixture of isoflavones was obtained by acid hydrolysis of isoflavone glycosides isolated from the products of soybean processing by a successive extraction with aqueous acetone and methanol. Homogeneous isoflavones genistein and daidzein were isolated from the aglycone mixture by adsorption chromatography and identified by spectral and chromatographic methods. The effect of both isoflavones on lipid peroxidation of soy phospholipids in multilamellar vesicles was studied at various concentrations. These aglycones were found to inhibit the formation of lipid hydroperoxides and malonic dialdehyde at the concentrations as low as 1 mM.