[The relationship between the level of Lр(а) and the prevalence of atherosclerosis among young patients].

BACKGROUND: Hyperlipoproteinemia (a) is an independent and cause risk factor for atherosclerotic cardiovascular diseases (ASCVD). The correlation between lipoprotein (a) Lp(a) and inflammation in the vessel wall was actively studied during the past few years. C-reactive protein (CRP) plays an important role in ASCVD. AIM: To analyze the relationship between hyperlipoproteinemia (a), inflammatory markers, and the early development of stenosing atherosclerosis (AS) in several vascular pools. MATERIALS AND METHODS: 76 patients, 55 men aged 18 to 55 years and 21women 18 to 60 years, with the results of instrumental examination of coronary, carotid and lower extremities vascular pools were enrolled. Three groups: with stenosing (50%) AS of only one (group 1, n=29); two or three (group 2, n=21) vascular pools. 26 patients without coronary heart disease and AS were included in the control group. All patients in groups 1 and 2 and 65% of those in the control group took statins. The concentrations of Lp(a), CRP, lipids and blood count were determined. RESULTS: The patients of the three groups did not differ in age. In the groups with AS (79% in group 1 and 85% in group 2), there were more men (relative to 54% in the control group). Diabetes mellitus was more common only in patients with multifocal AS. The absolute number of blood monocytes and leukocytes, the neutrophil-lymphocyte ratio, as well as Lp(a) level were higher in patients of groups 1 and 2 relative to the control. The maximum Lp(a) level (median [25%; 75%]) was observed in patients with lesions of two or more vascular pools vs the control group (49 [4; 96] mg/dL, vs 10 [4; 21] mg/dL, p=0.02). The CRP level was significant elevated in patients from group 2 7.2 [4.0; 9.7] mg/L, relative to group 1 2.5 [1.0; 4.7] mg/L, and the control group 2.9 [1.2; 4.9] mg/L, p0.05. The Lp(a) and CRP concentration, or the presence of diabetes mellitus in patients, regardless of other risk factors, were associated with severe stenosing AS in young and middle age. CONCLUSION: An elevated concentration of Lp(a) (30 mg/dL) determines the presence of both isolated and multifocal stenosing AS in the examined patients. A simultaneous increase in the concentration of both Lp(a) and CRP, as well as the presence of diabetes mellitus, are associated with the premature development of stenosing atherosclerotic lesions in several vascular regions at once. Measurement of these predictors in young and middle-aged patients makes it possible to use them as biochemical markers to assess the likelihood of multifocal lesions of the vascular pool.

Circulating Complex of Lipoprotein(a) and Proprotein Convertase Subtilisin/Kexin Type 9 in the Serum Measured by ELISA.

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.

[Association of lipoprotein (a) with ischemic stroke and stenotic carotid atherosclerosis]. / Sviaz' lipoproteida(a) s ishemicheskim insul'tom i stenoziruiushchim aterosklerozom sonnykh arterii.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor of coronary heart disease and its complications. Meanwhile data about the role of Lp(a) in development of ischemic stroke are controversial. AIM: To investigate the association of Lp(a) with atherothrombotic ischemic stroke and stenotic (≥50%) atherosclerosis of carotid arteries. MATERIAL AND METHODS: The study included 490 patients (mean age 60 years, 53% male). The first group comprised 157 patients with ischemic stroke, the second group 68 patients with isolated stenotic atherosclerosis of carotid arteries, but without significant lesion of coronary and low limbs arteries. The control group included 265 patients without stroke, myocardial infarction, stenotic atherosclerosis of coronary, carotid and low limbs arteries according to instrumental examinations. The levels of Lp(a) and lipids were measured in blood serum of all patients. RESULTS: Lp(a) concentration was significantly higher in patients of the first and second groups in comparison with the control group (median [interquartile range]): 24 [9; 48], 20 [8; 55] vs 13 [5; 27] mg/dl, respectively (p<0,05 in both cases). Hyperlipoproteinemia(a) (Lp(a) ≥30 mg/dl) was more frequent in the group with stroke, stenotic atherosclerosis of carotid arteries, than in the control group: 43%, 40% vs 22% (p<0.01 in all cases). In patients with hyperlipoproteinemia(a), odds ratio (OR) for ischemic stroke was 2.7 (95% confidence interval (CI) 1.7-4.1), and OR for stenotic atherosclerosis of carotid arteries was 2.3 (95% CI 1.3-4.0) compared to the patients with Lp(a) level <30 mg/dl (p<0.01 in both cases). In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, smoking and Lp(a) concentration, the hyperlipoproteinemia(a) was associated with ischemic stroke and isolated stenotic carotid atherosclerosis. In the group with severe carotid atherosclerosis, 16 patients (24%) had ischemic stroke. Lp(a) concentration in these patients was higher 36 [20; 59] mg/dl, than in the patients with isolated carotid atherosclerosis without stroke 15 [7; 54] mg/dl (p=0.04). Other risk factors of atherosclerosis did not differ in patients with or without ischemic stroke. CONCLUSION: The study shows the association of elevated level of Lp(a) with ischemic stroke and isolated stenotic atherosclerosis of carotid arteries. In the presence of isolated stenotic carotid atherosclerosis, the median of Lp(a) concentration was significantly higher in patients with ischemic stroke than in patients without stroke.

[Lipoprotein(а) Level, Apolipoprotein(а) Polymorphism аnd Autoаntibodies Against Lipoprotein(а) in Patients with Stenotic Cаrotid Atherosclerosis].

Аim. Comparative assessment of respiratory indicators according to multifunctional monitoring (PFM) with the recommended standard for a complete polysomnographic study and an assessment of the effect of blood pressure (BP) measurements in PFM on sleep quality. Triаls on the аssociаtion of Lp(а) and cаrotid аtherosclerosis аre limited. The аim of the study wаs to investigаte the аssociаtion of Lp(а), аpolipoprotein(а) [apo(а)] polymorphism аnd аutoаntibodies to Lp(а) with stenotic (≥50%) cаrotid аtherosclerosis in dependence on CHD presence. Materials and methods. The study included 785 pаtients аt the аge from 21 to 92 with dаtа of instrumentаl exаmination of coronаry, cаrotid аnd lower limbs аrteries. Stenotic cаrotid аtherosclerosis wаs diаgnosed in 447 pаtients who were divided into two groups depending on presence (n=344) or аbsence (n=103) of CHD. The control group comprised of 338 pаtients without stenotic аtherosclerosis of coronаry, cаrotid аnd lower limbs аrteries. In the blood serum of pаtients levels of Lp(а), аutoаntibodies to Lp(а) were determined аnd аlso аpo(а) phenotyping wаs conducted. Results. There were more mаles, higher аverаge аge аnd frequency of hypertension, type 2 diаbetes mellitus, smoking, Lp(а) concentrаtion (mediаn [interquаrtile rаnge]): 30 [11; 63] vs. 14 [5; 30] mg/dl, p<0.01) in the group with stenotic cаrotid аtherosclerosis in compаrison with control group. Besides, Lp(а) level wаs higher in CHD subgroup thаn in pаtients with stenotic cаrotid аtherosclerosis without CHD: 32 [12; 72] vs. 24 [8; 50] mg/dl, respectively, p=0.01. Elevаted (≥30 mg/dl) Lp(а) level, low moleculаr weight аpolipoprotein(а) [(LMW аpo(а)] phenotype were аssociаted with stenotic cаrotid аtherosclerosis (odds rаtio (OR) 2.9; 95% confidence intervаl (CI) 2.1-4.0, p<0.01 аnd OR 2.3; 95% CI 1.6-3.4, p<0.01, respectively). Logistic regression аnаlysis showed independent аssociаtion of elevаted Lp(а) level аnd LMW аpo(а) phenotype with stenotic cаrotid аtherosclerosis both in the presence аnd absence of CHD. The level of IgM аutoаntibodies to Lp(а) wаs higher in control group thаn in pаtients with stenotic cаrotid аtherosclerosis, p=0.02. Conclusion The level of Lp(a) ≥30 mg/dl and low molecular weight phenotype of aprotein(a) are predictors of stenotic atherosclerosis CA, regardless of the presence of coronary heart disease and other risk factors, while a reverse relationship was found between the level of autoantibodies of the IgM class against Lp(a) and the severity of atherosclerosis CA.

[The Relationship of the Concentration of Lipoprotein(a) and Markers of Inflammation with Multifocal Atherosclerosis in Women].

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 °Ð¡ 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.

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.

Atherosclerosis of brachiocephalic arteries and arterial stiffness in patients with breast cancer.

Cardiovascular toxicity is one of the important problems of clinical oncology. Atherosclerosis progression was demonstrated in patients with cancer and chemotherapy.Te aim - to evaluate the vascular wall characteristics and to determine the predictors of AS of brachiocephalic arteries progression during anticancer therapy in patients with breast cancer. METHODS: Te study involved 43 patients with newly diagnosed breast cancer (BC) (II-III stage) with overexpression of HER2; median age 50 (40;57) years. All patients underwent neoadjuvant drug therapy with antracyclines, taxanes and trastuzumab followed by surgery, radiation and hormone therapy according to the indications. Before anticancer therapy the general clinical examination was conducted and lipid profle, plasma lipoprotein (a) [Lp(a)] level, titres of autoantibodies IgM and IgG to lipoproteins and their oxidized derivatives were estimated. Te vascular wall stiffness (pulse wave velocity on the carotid-femoral (PWVcf) and shoulder-ankle (PWVsa) segments, the central pressure, carotid intima-media thickness (CIMT) and the degree of stenosis of the brachiocephalic arteries) were determined at baseline and at each stage of anticancer therapy. Te atherosclerosis progression was determined if the new stenosis (≥15%) or increase of preexisting stenosis (≥5%) were revealed; CIMT increase ≥ 0.1 mm. Te parameters of cellular immunity (peripheral blood lymphocyte phenotyping via direct immunofluorescence and flow cytometry), lipid spectrum parameters, serum concentration of Lp (a), autoantibodies IgM and IgG against lipoproteins and their oxidized derivatives, as well as PWVсf and PWVsa were assessed in 17 BC patients before the onset of neoadjuvant therapy and in 20 healthy women. RESULTS: BC patients and healthy women were comparable in traditional cardiovascular risk factors but differed in PWVsa and PWVcf levels (p<0.05). In BC patients the activation of T-cell immunity with the stimulation of both subpopulations with pro-inflammatory and regulatory properties was observed (p<0.05). Te direct correlations between the content of activated T-lymphocytes (T-act), T-helpers (T) 1 and PWVsa (p<0.05), as well as T-act, T1 and T2 and PWVcf (p<0.05) were revealed in the general group. Te decrease of systolic blood pressure (SBP), central SBP (SBPc), central diastolic blood pressure (DBPc), PWVcf and PWVsa levels accompanied with a temporary heart rate increase were observed during anticancer therapy; SBP, SBPc, PWVcf levels restored by the end of the follow-up period. Te CIMT increase was detected in 22 (51%), and the atherosclerosis progression in 26 (60%) BC patients during anticancer therapy. Lp (a) level above 12.8 mg/dl was associated with CIMT increase (p<0.05). Age > 48 years and radiation therapy were risk factors for CIMT increase and atherosclerosis progression (p<0.05), respectively. CONCLUSIONS: Te vascular stiffness is increased in BC patients, which is associated with the activation of effector subpopulations of T-lymphocytes and the elevation of circulating level of both pro-atherogenic and anti-atherogenic T-cells. Te level of Lp (a) above 12.8 mg/dl is associated with atherosclerosis progression, which requires further research. Age and radiation therapy are the risk factors for atherosclerosis progression during anticancer therapy.

Low Blood Content of IL-10-Producing CD4+ T Cells as a Risk Factor for Progression of Coronary Atherosclerosis.

In a 2-year prospective study, prognostic significance of the blood content of IL-10-producing CD4+ T lymphocytes for progression of coronary artery atherosclerosis was assessed. Patients with verified stable angina (n=36) admitted for scheduled coronary angiography and coronary stenting were enrolled. The blood levels of CD4+FoxpP3+ Treg, CD4+IFNγ+ Th1, CD4+IL17+ Th17, CD4+IL10+ cells, sCD25, IL-10, IL-17, C-reactive protein, and lipoprotein (a) were assayed before endovascular interventions. The blood content of CD4+IL10+ T cells below 3.3% was associated with progression of coronary artery atherosclerosis (OR 12.0 (2.3, 61.0), sensitivity 77%, specificity 78%, p=0.003). No differences in other immunological parameters and common atherosclerosis risk factors in the groups were revealed. We hypothesize that the content of CD4+IL10+ T cells can be an important predictive marker for the progression of coronary atherosclerosis.

The Association of Lipoprotein(a), Apolipoprotein(a) Phenotypes and Autoantibodies to Lipoprotein(a) With Lower Extremity Artery Disease.

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 ankle-brachial 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 (p<0.001 in all the cases). The level of Lp(a) was significantly higher in the main group compared to control group: 35 [14; 67] mg / dl vs. 14 [5; 32] mg / dl, p<0,001. ROC analysis demonstrated that the level of Lp(a) ≥26 mg / dl was associated with LEAD (sensitivity 61 %, specificity 70 %). The prevalence of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype were higher in the main group in comparison with the control group: 61 % vs. 30 % and 48 % vs. 26 % respectively (p<0.001 in the both cases). The odds ratio of LEAD in the presence of Lp(a) ≥26 mg / dl was 3.7 (95 % confidence interval (CI), 2.6-5.1, p<0.001) and in the presence of LMW apo(a) phenotype was 2.6 (95 % CI, 1.7-4.0, p<0.001). In logistic regression analysis adjusted for age, sex, hypertension, smoking, diabetes, both Lp(a) and LMW apo(a) phenotype were independent predictors of LEAD when included separately. The level of IgM autoantibodies to Lp(a) was significantly higher in the control group compared to the patients with LEAD (p=0.01). Concentration of IgG autoantobodies to Lp(a) and LDL in the plasma did not differ essentially in the both groups. CONCLUSION: 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.

The association of lipoprotein(a) and apolipoprotein(a) phenotypes with peripheral artery disease.

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<0.01 in all cases. Lp(a) level was higher in the group I than in the other groups (p<0.05). The prevalence of elevated Lp(a) level (≥ 30 mg/dl) was significantly higher in groups I, II, III than in control group: 54%, 50%, 43% respectively vs. 30%, p<0.01 in all cases. The prevalence of Lp(a) ≥ 30 mg/dl was more frequent in the group with PAD and CHD than in the group with CHD and without PAD (p=0.02). The odds ratio (OR) of PAD in the presence of elevated Lp(a) level was 1.9 (95%CI, 1.4-2.5, p<0.01). Low molecular weight (LMW) apo(a) phenotype was met more frequently in groups I, II, III compared to group IV: 46%, 56%, 52% respectively vs. 28%, p<0.01. LMW apo(a) in the patients without CHD was associated with PAD (OR 3.3; 95% CI, 1.6-6.8, p<0.01), and there was no association with the patients with CHD. In logistic regression analysis adjusted for age, sex, hypertension, obesity, smoking, diabetes, LDL-C, Lp(a) and LMW apo(a) phenotype were independent predictors of PAD when included separately. CONCLUSION: Elevated level of Lp(a) and LMW apo(a) phenotype are independent risk factors of PAD. The level of Lp(a) in the patients with PAD and CHD was higher than in the case of isolated lesion of each vascular pool. Higher level of Lp(a) is associated with more severe atherosclerosis involving more than one vascular pools.

[Subpopulation Composition of CD4+ T-lymphocytes as Factor Contributing to the Progression of Atherosclerosis of Carotid Arteries].

AIM: to assess prognostic significance of blood content of regulatory and effector T-lymphocytes for progression of atherosclerosis (AS) of carotid arteries. MATERIAL AND METHODS: We enrolled in this study 33 men with various severity of carotid AS. Carotid artery duplex scan was done at admission and in 1 year after enrollment. AS progression was defined as appearance of novel stenosis in common or internal carotid artery or more or equal 5% increase of preexisting stenosis. Peripheral blood lymphocyte phenotyping was performed by direct immunofluorescence and flow cytometry at the enrollment. T-helpers (Th) 1 were identified as CD4+IFNgamma+ cells, Th2 - CD4+IL4+, activated T-cells (T-act) - D4+CD25lowCD127high, regulatory T-cells (T-reg) - D4+CD25highCD127 low and CD4+FoxP3+, Th17 - CD4+IL17a+ cells. RESULTS: Progression of carotid AS was observed in 18 patients. Basal values of Th17 were higher while ratio T-reg/Th17 was lower in patients with compared with those without AS progression. ROC-analysis showed high sensitivity and specificity of blood levels of Th17, T-act and T-reg/Th17 ratio for carotid AS progression during one year in patients with low density lipoprotein cholesterol (LDLCH) level below 3.5 mmol/l. CONCLUSION: The imbalance between circulating levels of regulatory T-cells and T-helpers 17 with the prevalence of proinflammatory T-helpers 17 may reflect a predisposition for carotid AS progression, what also refers to patients with relatively low LDLCH.

Characteristics of Lipoprotein(a)-Containing Circulating Immune Complexes as Markers of Coronary Heart Disease.

We studied the composition of circulating immune complexes precipitated in the presence of various concentrations of polyethylene glycol in patients with coronary heart disease (CHD) and high concentration of lipoprotein(a) - Lp(a). Precipitation of highly purified Lp(a) preparation with polyethylene glycol was evaluated. The contents of Lp(a), autoantibodies to Lp(a), IgG, and IgM in circulating immune complexes isolated from the sera of donors and CHD patients with normal and high levels of Lp(a) were measured. Circulating immune complexes containing Lp(a) were detected in the plasma of CHD patients with high Lp(a) concentrations. The presence of high concentrations of Lp(a), autoantibodies to Lp(a), and circulating immune complexes in CHD patients suggests that immunological factor contributes to high atherothrombogenicity of Lp(a).

[Lipoprotein(a), its autoantibodies, and circulating T lymphocyte subpopulations as independent risk factors for coronary artery atherosclerosis]. / Lipoproteid(a), autoantitela k nemu i tsirkuliruyushchie subpopulyatsii T-limfotsitov kak nezavisimye faktory riska ateroskleroza koronarnykh arterii.

AIM: To study the role of lipoprotein(a) [Lp(a)] as a potential autoantigen causing the activation of immunocompetent cells in atherosclerosis. SUBJECTS AND METHODS: A total of 104 men with stable coronary artery (CA) disease and different degrees of progressive coronary atherosclerosis were examined. Clinical blood analysis was carried out and lymphocyte subpopulations (CD4+, Th1, Th17, and Treg) were determined using immunofluorescence and flow cytometry. In addition, the indicators of blood lipid composition, Lp(a), autoantibody (autoAb) titer to Lp(a), and low-density lipoproteins (LDL), and the lymphocyte activation marker sCD25 were also measured. RESULTS: The Lp(a) level was shown to predict the severity of CA lesions (ß=0.28, p<0.05), regardless of age, the level of cholesterol, different T-lymphocyte subpopulations, sCD25, and autoAb. A combination of the concentration of Lp(a) above 11.8 mg/dl, that of Th17 over 11.4∙103 cells/ml and the reduced levels of regulatory T cells and IL-10-producing CD4+ T cells showed a manifold increase in the risk of severe and progressive CA atherosclerosis. There was a direct correlation of the blood level of Th1 with that of IgG autoAb specific to all atherogenic apoB-containing lipoproteins, including Lp(a). There was an inverse correlations of the lymphocyte activation marker sCD25 with IgM anti-Lp(a) autoAb titers (r=-0.36; p<0.005), but this was less significant with autoAbs to native and oxidized LDL (r=-0.21 and r=-0.24; p<0.05, respectively). CONCLUSION: The slightly elevated Lp(a) concentration along with changes in the level of T lymphocyte subpopulations was first shown to significantly potentiate the risk of progressive and multiple CA lesion in the examinees. The correlation of IgM anti-Lp(a) autoAb with the lymphocyte activation marker sCD25 and that of IgG anti-Lp(a) autoAb with Th1 have demonstrated that Lp(a) is involved in the autoimmune inflammatory processes in atherosclerosis.

[Autoantibodies against lipoprotein(a) in patients with coronary heart disease].

OBJECTIVE: Lipoprotein(a) - Lp(a) is an independent risk factor of atherosclerosis and its complications. In spite of the long period of Lp(a) research there is no complete understanding of its physiological role and atherogenic action. The goal of this study was to investigate the presence in human plasma of circulating autoantibodies to Lp(a) belonging to different classes of immunoglobulins, and to elucidate their relationship to the presence and severity of coronary atherosclerosis in middle aged patients with coronary heart disease. MATERIAL AND METHODS: Autoantibodies to Lp(a) and LDL level were measured in 97 men with quantitative angiography data. Among these patients 17 had intact vessels and 80 had stenoses >50% in 1 or more large coronary arteries. RESULTS: Lp(a) level in patients with coronary atherosclerosis (CA) was significantly higher (median 19.0 [95%CI 12.9-27.3] mg/dl) than in patients without CA (median 10.2 [95%CI 4.5-18.3] mg/dl, p=0.05). Level of IgG autoantibodies to Lp(a) was also elevated in patients with verified CA (264 ± 188 and 187 ± 59 RLU, respectively, p=0,003). Correlation analysis showed significant association between Lp(a) concentration and presence of CA (r=0.20, p=0.05). Level of antibodies against Lp(a) correlated with the quantity of affected coronary arteries (r=0.27, p=0.008). CONCLUSION: Plasma concentration of Lp(a) as well as elevated level of autoantibodies to Lp(a) were associated with the presence and severity of coronary atherosclerosis in examined patients.

[The immune-enzyme analysis based on chimeric molecule and oligopeptide fragmentations to detect autoantibodies to beta-adrenergic receptor in patients with dilation cardiomyopathy].

The article deals with specification of technique of immune-enzyme analysis to detect autoantibodies to beta-adrenergic receptors (beta1-AP) using compound of oligopeptids representing the fragmentations of extracellular sites beta1-AP and chimeric molecule of extracellular section of receptor This technique significantly exceeds the analogues defined in publications by its sensitivity and correlation with diagnosis.