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The journal "Ateroskleroz"

2019 year, number 2

1.
GUIDELINE ON THE MANAGEMENT OF BLOOD CHOLESTEROL: TOP 10 TAKE-HOME MESSAGES TO REDUCE RISK OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE THROUGH CHOLESTEROL MANAGEMENT


																								



2.
Internalisation of calcium phosphate and magnesium phosphate bions by endothelial cells utilising scanning electron microscopy and confocal microscopy

D.K. Shishkova, R.A. Mukhamadiyarov, E.A. Velikanova, Yu.A. Kudryavsteva, A.G. Kutikhin
Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy blvd., 6
Keywords: bions, calcium phosphate, hydroxyapatite, endothelium, atherosclerosis, internalisation, lysosomes

Abstract >>
Aim of the study was to investigate whether endothelial cells internalise magnesium phosphate and calcium phosphate bions. Material and methods. Magnesium phosphate and calcium phosphate bions synthesised through supersaturation of the culture medium with the respective salts were further added to the confluent cultures of primary human coronary artery endothelial cells for 4 h. Internalisation was evaluated by backscattered scanning electron microscopy (BSEM) and confocal microscopy. For BSEM, cells were fixed in 10% neutral phosphate buffered formalin, postfixed/stained by 2 % osmium tetroxide, dehydrated in a graded ethanol series, stained by 2% uranyl acetate, impregnated into acetone:epoxy resin (1:1) and into the fresh epoxy resin with its subsequent polymerisation, grinding, and polishing. Samples were then counterstained by lead citrate, sputter coated with carbon, and visualised utilising BSEM. Confocal microscopy was conducted after exposure of endothelial cells to FITC-labeled magnesium phosphate bions or calcein-labeled calcium phosphate bions with the following staining by a pH sensor LysoTracker Red and nuclear stain Hoechst 33342. Results. All types of bions were internalised by endothelial cells within 4 h. BSEM after long-term postfixation/staining by osmium tetroxide and uranyl acetate, embedding into epoxy resin and counterstaining by lead citrate visualised multiple black electron-dense mineral inclusions which were not detected both within the control cells and in the intercellular space. Confocal microscopy also detected internalised MPB and CPB in cytosol and lysosomes. Conclusion. BSEM visualised MPB and CPB internalised by endothelial cells after 4 h exposure while confocal microscopy detected their colocalisation with lysosomes. MPB is an appropriate comparison group to study the specificity of CPB-related pathogenic effects as both of these bion types have close physico-chemical properties and are similarly internalised.
																								



3.
CLINICAL PREDICTIVE VALUE OF TISSUE INHIBITOR OF METALLOPROTEINASE-1 IMYOCARDIAL REMODELING DEVELOPMENT IN PATIENTS HAVING Q-WAVE MYOCARDIAL INFARCTION

A.S. Vorobyev1,2, L.V. Kovalenko1, K.Yu. Nikolaev2,3, I.A. Urvantseva1,2, T.O. Simonyan1, M.I. Rudenko1
1Surgut State University, 628412, Surgut, Lenin av., 1
2District Cardiology Clinic Center of Diagnostics and Cardiovascular Surgery, 628403, Surgut, Lenin av., 69/1
3Research Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: myocardial infarction, myocardial remodeling, TIMP-1, prediction

Abstract >>
In this paper we thought to investigate clinical value of tissue inhibitor of metalloproteinase-1 (TIMP-1) in predicting left ventricular (LV) myocardial remodeling in patients having Q-wave myocardial infarction (Q-wave MI). We demonstrated that TIMP-1 serum level clearly corresponds to degree of postinfarction LV myocardial remodeling. In patients who had serum concentrations of TIMP-1 over the established cut-off value (144.0 ng/ml), the risk of post-infarction LV remodeling was 3.33 times higher than in individuals who had TIMP-1 levels lower this value. Thus, TIMP-1 is a reliable prediction biomarker of adverse left ventricular myocardial remodeling in Q-wave MI.
																								



4.
FEATURES OF FATTY ACID COMPOSITION OF ERYTHROCYTE MEMBRANE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION (PILOT STUDY)

M.V. Kruchinina1, A.A. Gromov1, M.V. Parulikova1, A.V. Rabko1, M.V. Shashkov2, A.S. Sokolova3, V.N. Kruchinin4
1Research Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 10
2G.K. Boreskov Institute of Catalysis of SB RAS, 630090, Novosibirsk, Akademik Lavrentiev av., 5
3N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of SB RAS, 630090, Novosibirsk, Akademik Lavrentiev av., 9
4A.V. Rzhanov Institute of Semiconductor Physics of SB RAS, 630090, Novosibirsk, Akademik Lavrentiev av., 13
Keywords: resistant arterial hypertension, fatty acids, membrane of erythrocytes

Abstract >>
This study aims to evaluate peculiarities of composition and level of fatty acids (FAs) in eruthocytemembranes (EM) of patients with resistant arterial hypertension (RAH) which could be applied in diagnosis of pathogenic aspects of the disease, development of new therapeutic targets. 24 males with controlled arterial hypertension (CAH) (stage 2), 20 subjects with RAH (535.7 years), 22 healthy males were included into the study. The Agilent 7000B (USA) GC system was applied to study FAs composition. The patients with CAH demonstrated increase in ratio of saturated, monoenoic FAs as well as decrease of polyenoic ones. Significant increase was registered in levels of C14:0, C17:0, C18:0, C20:0, C18:1; 9 (p < 0.01-0.05). We registered decrease in ratio of n6 unsaturated FAs: (C18:2, C20:4, C22:4) n6, (p < 0.01-0.05). Patients with RAH displayed increase in levels of C15:0, 16:0 FAs, oleic, midic ones (p = 0.03-0.05). The registered increased level of C20:3 n9 would compensate synthesis which would take place in cases of deficit of n6, n3 polyunsaturated FAs (PUFA). Increase in ratio (C20:3/C18:1) n9 tends to evoke active synthesis of substrates for formation of prostacyclins, thromboxanes which are known to possess vasoconstrictive properties. Changes in PUFA tended to be most highly pronounced, especially in cases of n3 (C22:5, C22:6; p < 0.01). Patients with RAH demonstrated 2.1-time decrease of total n3 PUFA as compared to subjects with CAH. Increase of arachidonic acid level by up to 37.8 % served as an outstanding finding in patients with RAH. That was the sign of deficit of n3 PUFA. Disbalance in structure of n3, n6 was seen in decreased n3/n6 ratio (p < 0.01). Patients with RAH demonstrated accumulation of saturated, polyunsaturated n6 FA with deficit of n3 PUFA in erythrocyte membranes. This speaks in favor of decrease in fluidity of cellular lipid bilayer, inhibition of binding ligands with the receptor, activity of enzymes bound with membrane, including PIEZO1 and PIEZO2 proteins (responsible for sensitivity to pressure). Increase in disorganization of lipid components of cellular membrane causes progression of hypertension with further development of resistant forms, what should be considered an important link in pathogenesis and target for therapy.
																								



5.
ASSOCIATION BETWEEN coronary heart disease AND gallstone disease (EPIDEMIOLOGICAL STUDY)

I.N. Grigorieva1,2, Yu.I. Ragino1, T.I. Romanova1, S.K. Malyutina1
1Research Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 1
Keywords: coronary heart disease, gallstone disease, conventional risk factors

Abstract >>
The aim of the study was to evaluate in the epidemiological study the possible association of coronary heart disease (CHD) and gallstone disease (GSD) in women aged 25-64 years and in men aged 35-54 years, and assess the possible impact on it of certain conventional risk factors (body mass index (BMI), dyslipoproteinemia (DLP), the presence of arterial hypertension (AH) and of diabetes mellitus (DM) type 2) in women. In the frame of the WHO MONICA programs it was shown, that among the unorganized urban men population (n = 399) there was no significant relationship between the presence of «definite IHD and GSD: OR = 0.8 (95 % CI 0.1-6.4, p = 0.8). Among the unorganized urban women population (n = 870) a direct association of GSD with a «definite coronary artery disease was established: OR = 2.0 (95 % CI 1.1-3.4; p < 0.05), which did not depend on the presence or absence of AH (OR = 1.8; 95 % CI 1.01-3.1; p < 0.05), DLP (OR = 1.9; 95 % CI 1.1-3.6; p < 0,05) or DM type 2 (OR = 1.8; 95 % CI 1.03-3.6; p < 0.05), but disappeared when age and BMI were included in the analysis (OR = 1.5; 95 % CI 0,9-2.7; p > 0.05 and OR = 1.6; 95 % CI 0.9-2.9; p > 0.05, respectively).
																								



6.
COGNITIVE IMPAIRMENT IN THE ELDERLY AT FAMILY CASES OF ATHEROSCLEROSIS-ASSOCIATED DISEASES

A.V. Sukhanov
Research Institut of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: aging, cognitive functions, atherosclerosis-associated diseases, stroke, dementia

Abstract >>
The assessment of the cognitive testing success in the elderly (by the Mini-Cog test) depending on the presence of a burdened family anamnesis by stroke and dementia in the parents of the examined persons has been performed. 305 people were examined (participants of the health groups in the Regional Gerontological Center - continuous series): 31 (10.2 %) men and 274 (89.8 %) women. The average age of men was 71.4 7.2 years, women - 67.4 7.6 years. It was shown that the burdened family anamnesis by atherosclerosis-associated diseases (stroke and dementia) has a negative impact on the state of cognitive functions in the elderly.
																								



7.
ASSESSMENT OF PREVALENCE OF DISEASESOF THE BLOOD CIRCULATORY SYSTEM AMONG THE POPULATIONOF KRASNOYARSK KRAI

O.Yu. Kutumova
Krasnoyarsk Regional Center of Medical Prevention, 660049, Krasnoyarsk, Parizhskoi Kommuny str., 33
Keywords: incidence, blood circulatory system diseases, age features

Abstract >>
A research objective was to analyze the prevalence of blood circulatory system diseases (BCSD) with determination of their importance among other classes of diseases on the basis of the integrated assessment of indicators and also establishment of priorities of separate nosological groups of cardiovascular pathology at various age contingents of the population. According to official statistical data for 2016-2017 the incidence of the population of Krasnoyarsk Krai with the analysis of indicators of the general, primary negotiability and the persons staying on the dispensary registry, calculation of coefficients of relative importance and their integrated assessment is studied. Comparative characteristic of incidence of the separate age contingents of the population by 7 main nosological groups of diseases of the blood circulatory system is given. It is established that with increase in age there is an increase of the importance of this class of diseases which from the 10th place at children become the leading pathology in adult and elderly age groups when their specific weight of the importance changes according to 2.6 % up to 24.3 and 42.7 %. At the same time among children and teenagers basic diseases are heart troubles (except ischemic) and also existence at considerable number of patients of the increased arterial blood pressure (teenagers). At adult population of working-age the increased arterial blood pressure, coronary heart disease, cerebrovascular disease prevail, the defining 85.2 % of addresses of patients with BSK is most significant. 88.9 % of requests of the elderly population for medical care are connected with the same groups of diseases of BCSD. The carried-out analyses and the integrated assessment of BCSD prevalence in Krasnoyarsk Krai allowed to establish the importance of this class of diseases and to define priorities of separate nosological groups among various age contingents of the population. The received results are a basis for forming of strategy of the organization of medical care and determination of demand of medical technologies in the region.
																								



8.
CONTRAST ECHOCARDIOGRAPHY WITH ASSESSMENT OF MYOCARDIAL PERFUSION IN DIAGNOSIS OF NO-REFLOW PHENOMENON IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

D.V. Krinochkin, I.S. Bessonov, V.A. Kuznetsov, E.I. Yaroslavskaya, A.G. Takkand
Tyumen Cardiology Research Center, Tomsk National Research Medical Center of RAS, 625026, Tyumen, Melnikaite str., 111
Keywords: coronary heart disease, acute myocardial infarction, no-reflow phenomenon, contrast echocardiography, percutaneous coronary intervention, angiography

Abstract >>
Timely performed endovascular revascularization is the main modern method of treating for patients with acute myocardial infarction and elevated ST segment. In most cases, it is possible to achieve rapid recovery of coronary blood flow in the infarct related artery. Nevertheless, 10-40 % of patients manifest diminished myocardial reperfusion despite successful opening of the obstructed epicardial artery - so called the no-reflow phenomenon. The main angiographic features of hypoperfusion in the infarction zone are decrease in the degree of myocardial glow and/or blood flow by the TIMI scale. However, the use of angiographic criteria does not always allow accurate detection of developing no-reflow phenomenon. The presented case demonstrates the possibilities and potential benefits of contrast enhanced echocardiography in assessing the no-reflow phenomenon in a patient with acute myocardial infarction after revascularization.
																								



9.
LIPID, CARDIOVASCULAR AND PHARMACOGENETIC EFFECTS OF A COMMON VARIANT IN THE 1 GENE (rs2230806)

P.P. Malyshev1, G.P. Smirnov2, D.N. Nozadze1, I.V. Sergienko1
1National Medical Research Center of Cardiology of Minzdrav of Russia, 121552, Moscow, 3rd Cherepkovskaya str., 15A
2City Polyclinic 212 of the Moscow Healthcare Department, 119620, Moscow, Solntsevsky av., 11A
Keywords: ATP-binding cassette transporter A1, coronary heart disease, ABCA1 gene polymorphism, statins, R219K, rs2230806

Abstract >>
ATP-binding cassette transporters (ABC) are a family of proteins that function as transmembrane carriers of molecules using adenosine triphosphate (ATP) hydrolysis as an energy source. ABCA1 is a protein that functions as a «cholesterol pump in the removal of lipids from the cell and transfersthe cholesterol and phospholipids from the cell membrane to apolipoproteins for the subsequent formation of nascent high-density lipoproteins (HDL). The most common and one of the most studied is the nonsynonymous allelic variant rs2230806; however, the effects of this genetic polymorphism on atherosclerosis and lipid profile till now remain debatable. The phenotypic effects of this variant are opposite to those observed in the ABCA1 mutationheterozygous carriers, suggesting that this genetic variant is associated with increased ABCA1 function and reverse cholesterol transport. Meta-analyses confirmed the association of rs2230806 polymorphism with higher levels of HDL cholesterol and lower levels of TG and LDL cholesterol in the general population, which could mediate a decrease in the risk of coronary heart disease in allelic carriers. It is known that the relationship of rs2230806 variant with HDL levels and coronary heart disease is more stable and consistent in Asian populations than in European ones. Single pharmacogenetic studies show no effect of rs2230806 ABCA1 on the main lipotropic effect of statins, reduction of LDL-C, but indicate a positive reaction of HDL in one study. In practice, the detection of this genetic polymorphism, along with other ABCA1 allelic variants, can be used for screening of persons at higher risk of coronary heart disease with the early preventive measures in carriers of risk alleles.
																								



10.
MIRNA AS DIAGNOSTIC MARKERS OF ACUTE MYOCARDIAL INFARCTION AND HEART MUSCLE REMODELING

D.E. Ivanoshchuk1,2,3, A.S. Rozanov1, P.S. Orlov1,2,3, S.V. Mikhaylova1, E.V. Shakhtshneyder1,2,3, M.V. Kruchinina2, M.I. Voevoda1,2,3
1Federal Research Institute of Cytology and Genetics of SB RAS, 630090, Novosibirsk, Akademik Lavrentiev av., 10
2Research Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
3Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 2
Keywords: myocardial infarction, remodeling, miRNA, diagnostic markers, RNA, gene expression

Abstract >>
Cardiovascular diseases, in particular myocardial infarction (MI), are one of the most common causes of death in the world. Today, a significant problem for assessing of MI and post-infarction complications risks is the insufficient sensitivity and prognostic values of modern methods and markers. Therefore, the identification of new markers with high specificity and sensitivity is an important task. Recently, much attention has been paid to the study of extracellular RNAs, which are relatively stable in biological fluids. In this article, we overviewed some miRNAs, which are considered as potential markers for the diagnosis of MI and prediction of its adverse effects.
																								



11.
INFECTIONS, INFLAMMATION AND ATHEROSCLEROSIS

O.V. Reshetnikov1, S.A. Kurilovich1,2, Yu.P. Nikitin1
1Research Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
Keywords: atherosclerosis, bacteria, viruses, pathogenetic mechanisms

Abstract >>
Atherosclerotic cardiovascular diseases are the leading cause of death worldwide. In recent decades, the influence of many microorganisms involved (directly or indirectly) in provoking the process of atherogenesis, including cell adhesion, cytokine-associated damage, release of reactive oxygen species, etc. has been shown. Others, such as the influenza virus, can cause systemic inflammation that can damage vascular wall (for example, by cytokines and proteases). In addition, another indirect mechanism by which some infectious agents (such as Helicobacter pylori, Chlamydia pneumoniae, periodontal pathogens, etc.) that may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each pathogen can contribute to the development and progression of atherosclerosis, it is obvious that ongoing research and new data will be useful for improving our understanding of the infectious component of atherosclerosis.