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Purpose: to study relationship of lipoprotein(a) [Lp(a)], indicators of systemic inflammation and humoral immunity with severity of atherosclerotic involvement of various vascular beds in women.Materials and methods. We included in this study 148 women aged 69±11 years with results of instrumental investigation of coronary, carotid arteries, and arteries of lower extremities. According to results of coronary angiography and ultrasound study patients were distributed into two groups: with stenosing atherosclerosis (those with hemodynamically significant [>50%] atherosclerotic lesions in any of these vascular beds, n=108), and control (those without hemodynamically significant stenoses, n=40). In dependence of extent of atherosclerotic involvement patients with stenosing atherosclerosis were divided into subgroups: with lesions in one vascular bed (subgroup 1, n=44) and with lesions in two and more vascular beds (subgroup 2, n=64). All patients with stenosing atherosclerosis and 78% of control patients took statins. In all patients we measured lipid spectrum, Lp(a) concentration, C-reactive protein (CRP). Preparations of oxidized lipoproteins [oxLp(a)] were obtained by Cu2+-induced free radical oxidation at 37 °С for 3 hours. Titer of autoantibodies to Lp(a), LDL and their oxidized modifications was determined by enzyme-linked immunosorbent assay (ELISA). Concentration of low-density lipoprotein cholesterol corrected on cholesterol in Lp(a) (LDLCh corr) was calculated by Dahlen modification of Friedewald formula.Results. Stenosing atherosclerosis was diagnosed in 60 of 74 women (80%) with Lp(a) concentration above median - 33 mg/dl (in 38 multifical). Increase of blood serum Lp(a) concentration was associated with presence of isolated as well as multifocal atherosclerosis according to unifactorial, multifactorial, and logistic analysis, irrespective of other factors of risk and indicators of inflammation. According to results of logistic regression analysis increase of Lp(a) concentration by 1 mg/dl was associated with 1 % elevation of probability of appearance and development of multifocal atherosclerosis in women. Low level of class IgM autoantibodies to Lp(a) was linked with detection of stenosing atherosclerosis in any of 3 vascular beds (1st vs. 4th quartile of IgM autoantibodies concentration - OR 7.6., 95%CI 1.9-29.4; р=0.004) and had diagnostic significance. Indicators of systemic inflammation such as CRP and circulating immune complexes were high and had diagnostic significance for detection of multifocal atherosclerosis in studied women. However none of indicators was predictor of appearance of stenosing atherosclerosis according to data of logistic regression analysis.Conclusion. Elevated concentration of Lp(a) is an independent predictor of risk of development stenosing atherosclerosis in various vascular beds and appearance of multifocal irrespective of other risk factors, indicators of systemic inflammation, and factors of humoral immunity in women. Markers of inflammation, as well as IgM autoantibodies against Lp(a) have diagnostic value for detection of patients stenosing lesions ib one or several vascular beds.

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.

Aim. Lipoprotein(a) [Lp(a)] and low molecular weight (LMW) apolipoprotein(a) [apo(a)] phenotype are risk factors of сoronary heart disease and stroke. Data about the role of Lp(a) and phenotypes apo(a) in the development of lower extremity artery disease (LEAD) is scarce. The aim of our study was to assess the association of Lp(a), apo(a) phenotypes and autoantibodies to apolipoprotein B100 (apoB100) lipoproteins with LEAD.Materials and methods. The study included 622 patients (386 male and 236 female, average age 61±12 years), examined in the Department of Atherosclerosis of National Medical Research Center of Cardiology. Patients were divided into 2 groups: the main group included 284 patients with LEAD, 338 patients without significant atherosclerosis of coronary, carotid and lower limbs arteries formed the control group. LEAD was diagnosed as atherosclerotic lesions with at least one stenosis of low limb artery ≥50 % and ankle­brachial index ≤0.9. The concentration of Lp(a), lipids was measured in blood serum of all the patients, level of autoantibodies to apoB100 lipoproteins was measured in 247 patients, and apo(a) phenotypes were determined in 389 patients.Results.Patients with LEAD were older, were more frequently male, and had a greater prevalence of risk factors including hypertension, type 2 diabetes, smoking than the control group patients (pConclusion.The level of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype are independent predictors of LEAD, whereas the contribution of autoantobodies to Lp(a) in LEAD development is controversial.

Aim. Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and myocardial infarction. Data about the role of Lp(a) in the development of peripheral artery disease (PAD) is controversial and uncertain. The aim of the study was to evaluate the association between Lp(a), apolipoprotein(a) [apo(a)] phenotypes and PAD. Materials and methods. The study included 998 patients (707 male and 291 female, average age 60±12). The patients were divided into 4 groups depending on the presence or absence PAD and CHD: group I (n=188, PAD+CHD+), group II (n=78, PAD+CHD-), group III (n=407, PAD-CHD+), group IV (n=325, PAD-CHD-). Results. The level of Lp(a) was significantly higher in groups I, II, III in comparison with patients of control group (group IV): 34 [15; 80], 30 [10; 49], 22 [8; 60] mg/dl vs. 15 [6; 35] mg/dl respectively, p

The presence of a complex of lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) in the blood of healthy volunteers and patients with cardiovascular diseases was analyzed by ELISA. The levels of the complex varied in a wide range and did not depend on the concentrations of Lp(a) and PCSK9. Moreover, the complex was found not only in patients with cardiovascular diseases, but also in healthy volunteers, which can indicate physiological role of lipoprotein(a) as PCSK9 transporter.

Background Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). It has been recently shown that autotaxin (ATX), which breaks down lysophosphatidylcholine, derived from oxidized phospholipids, to lysophosphatidic acid, was strongly associated with CAVS. Purpose The aim of the study was to investigate the role of Lp(a) and ATX in CHD patients with and without CAVS. Methods The study included 438 patients (average age 66±11 years, men 310), 332 had CHD with ≥50% stenosis in at least one coronary artery according to angiography. CAVS was diagnosed with ultrasound. The control group consisted of 106 patients without CHD and CAVS. The concentrations of Lp(a), ATX, lipids and blood cells were measured for all the patients. Results CHD without CAVS (group I) was diagnosed in 287 patients, 45 patients had CHD and CAVS (group II). Patients in both groups were older than patients in the control group (75±8, 66±10 and 61±13 years respectively). ATX level was lower in group I (median [25; 75%]: 493 [406; 583] ng/ml) than in control group (544 [412; 655] ng/ml, p=0.02) or group II (553 [475; 609] ng/ml, p=0.003). Lp(a) was lower in control group (14.5 [5.5; 36.0] mg/dl) than in group I (25.6 [9.7; 58.5] mg/dl, p=0.0004) and group II (23.8 [9.9; 79.1] mg/dl, p=0.02). Elevated level of ATX was positively associated with CAVS in CHD patients, but negatively with CHD in patients without CAVS. We have shown that age, glucose level and neutrophil-lymphocytes index (NLI) could be predictors of CAVS in patients with CHD according to results of logistic regression analysis. Odds ratio of high (QIV) vs. low (QI) Odds ratio (95% confidence interval) Groups Autotaxin Lipoprotein(a) Neutrophil-lymphocytes index I vs. control 0.5 (0.3–0.9)* 2.7 (1.3–5.2)** 2.4 (1.3–4.6)* II vs. control 8.6 (1.1–70.1)* 3.4 (1.2–9.4)* 6.2 (2.2–16.9)** II vs. I 16.6 (2.1–131.1)** 1.3 (0.5–3.2) 2.5 (1.0–6.37)* *p Conclusion Elevated Lp(a) level is a predictor of CHD regardless of calcific aortic valve stenosis, whereas elevated concentration of autotoxin in CHD patients was associated with calcific aortic valve stenosis.

Background Controversial data have recently emerged about the role of obesity in the development of cardiovascular diseases, otherwise known as “Obesity paradox”. Autotaxin (ATX) hydrolyzes lysophosphatidylcholine to lysophosphatidic acid, a lipid mediator involved in pathological processes, including obesity. Purpose To investigate the association between obesity and stenotic atherosclerosis of different vascular territories. Methods The study included 1225 patients with results of instrumental examination of coronary, carotid and lower limbs arteries. Stenotic atherosclerosis (≥50%) in any vascular bed was diagnosed in 889 patients. Results The patients were divided into two groups depending on body mass index (BMI) (table). The groups were comparable on age, lipids and frequency of CHD. The obesity negatively associated with lower extremity artery disease (LEAD) (odds ratio (OR) 0.51; 95% CI 0.36–0.72, p Characteristics of study groups Parameters Control, BMI Conclusion “Obesity paradox” was observed in the patients with LEAD, CHD and multifocal atherosclerosis and it could be associated with lysophosphatidic acid pathway.

Two fragments corresponding to the 125-133 and 206-218 sequences of a molecule of the beta(1) adrenoreceptor (autoantibodies to this protein are often found in patients with dilated cardiomyopathy) were synthesized by the solid phase method with the use of Fmoc technology. Two new conformational antigens were prepared by directed (regioselective) and undirected (spontaneous) formation of intramolecular and intermolecular disulfide bridges between the corresponding cysteine residues of the synthesized peptides. One of these antigens consisted of a mixture of disulfide isomers, and another antigen was an isomer with a natural arrangement of S-S bridges. Immunosorbents were obtained by immobilization of the synthesizes antigens on the bromocyanogenactivated sepharose and applied to the removal of autoantibodies in a beta(1)-adrenoreceptor from the blood plasma of patients. We demonstrated that the sorbents on the basis of the conformational antigens were more effective in comparison with those containing linear peptide precursors.

The observance of the Gibbs-Konovalov law is proved for all complex singular points of two-phase multicomponent systems.

It is proved that the Gibbs-Konovalov law is valid for all simple singular points of two-phase multicomponent systems.