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2015 year, number 3

Resistant hypertension: some aspects of pathogenesis

M.V. Kruchinina1, A.A. Gromov1, Ya. Sh Shvarts1, A.V. Rabko1, V.A. Baum1, V.M. Generalov2, V.N. Kruchinin3, S.V. Rykhlitskiy3, V.A. Volodin3
1FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
2State Scientific Center of Virology and Biotechnology «Vector», 633159, Kol’tsovo, Novosibirsk
3A.V. Rzhanov Institute of semiconductor physics SB RAS, 630090, Novosibirsk, Academik Lavrent’ev av., 13
Keywords: резистентная артериальная гипертензия (РАГ), гемоглобин, Раман-спектроскопия, ЯМР-спектроскопия, диэлектрофорез эритроцитов, resistant arterial hypertension, hemoglobin, Raman spectroscopy, NMR spectroscopy, dilectionis of red blood cells

Abstract >>
The work was devoted to studying the content of hemoglobin complexes, the level of energy-rich compounds, their relationship with the viscoelastic parameters of red blood cells in patients with resistant hypertension to identify possible pathogenetic features of the disease. Analysis of the processes have carried out on the basis of the methods of Raman spectroscopy (Raman), Nuclear Magnetic Resonance spectroscopy (NMR) and the method of Dielectrophoresis of erythrocytes (DEF) in a Non-Uniform Alternating Electric Field - effective, sensitive, non-destructive methods of investigation of different environments, proven in studies biological objects. Studies conducted in erythrocytes groups of subjects with arterial hypertension, including - resistant (42 people) and a comparison group (23 persons). The observed reduction in reserves of nitric oxide inside red blood cells, reducing its bioavailability associated with changes in the level and composition of intracellular energy compounds, viscoelastic parameters of red blood cells are probably one of the pathogenetic factors for the development of resistant hypertension and target for therapeutic intervention.


N.P. Sudakov1,2,3, I.V. Klimenkov3,4, T.P. Popkova3, S.B. Nikiforov2, O.A. Goldberg2, S.A. Lepekhova1,2, K.A. Apartsin1,2, A.I. Katyshev5, Yu.M. Konstantinov3,5
1Irkutsk Scientific Center SB RAS, 664033, Irkutsk, Lermontov str., 134
2Irkutsk Scientific Center of Surgery and Traumatology, 664003, Irkutsk, Bortsov Revolyutsii str., 1
3Irkutsk State University, 664003, Irkutsk, Karl Marks str., 1
4Limnological Institute SB RAS, 664033, Irkutsk, Ulan-Batorskaya str., 3
5Siberian Institute of Plant Physiology and Biochemistry, 664033, Irkutsk, Lermontov str., 132
Keywords: дислипопротеидемия, атеросклероз, С-реактивный белок, свободно циркулирующая митохондриальная ДНК, dyslipidemia, atherosclerosis, C-reactive protein, free circulating mitochondrial DNA

Abstract >>
The aim of research: the studying of blood lipid spectrum, C-reactive protein concentration, and free circulating mitochondrial DNA changes in the course of aorta atherosclerosis development in early steps of high-cholesterol diet in experiment. Material and methods. Dyslipidemia was induced by high-cholesterol diet in rabbits “Chinchilla”. The C-reactive protein level and lipid spectrum was analyzed with Beckman synhron 4 multianalyzer (Beckman coulter, USA). The mitochondrial DNA level was registered by real-time PCR. The ultra structure of aorta surface was studied by scanning electron microscopy. Results. It was shown that in the blood of experimental animals is formed the Beckman imbalance of atherogenic and antiatherogenic cholesterol fractions (on 2 days of dyslipidemia) and iselevated the C-reactive protein level (on the 8 days). Concurrently, on the 16 days of study, we registered the leucocyte adhesion on the aorta surface in the areas of connections with arteria, which could be focuses of atherosclerotic plaque development. The level of free circulating mitochondrial DNA showed the tendency to 3-fold elevation in comparing with control. However, this data predetermined the prospects of blood plasma mitochondrial DNA level studying on the more late stages of dyslipidemia. Conclusion. In the whole, the detected complex of biochemical disturbances of blood and ultrastructural changes of aorta surface in the course of early steps of high-cholesterol diet maybe prospective model of early events of atherosclerosis for pre-clinical translational research in the development of new technologies for diagnostics, prophylaxis, and treatment of lipid metabolism disturbances and atherosclerosis.


A.V. Ponasenko1, M.V. Khutornaya1, A.G. Kutikhin1, I.I. Zhidkova1, A.S. Golovkin2, O.L. Barbarash1
1Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy blvd., 6
2Federal North-West Medical Research Centre, 197341, St. Petersburg, Akkuratov str., 2
Keywords: ишемическая болезнь сердца, атеросклероз, врожденный иммунитет, TLR, генные полиморфизмы, coronary artery disease, atherosclerosis, innate immunity, Toll-like receptors, gene polymorphisms

Abstract >>
Study aim: To investigate an association of the Toll-like receptor (TLR) gene polymorphisms with the risk of coronary artery disease (CAD). Materials and Methods: We recruited 702 consecutive Russian patients with CAD and 300 healthy blood donors who were residents of Western Siberia (Kemerovo Region). We investigated eight polymorphisms within four genes: TLR1 (rs5743551, rs5743611), TLR2 (rs3804099, rs5743708), TLR4 (rs4986790, rs4986791), and TLR6 (rs3775073, rs5743810). Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. Results: C/C genotype of rs5743551 polymorphism and C/G genotype of rs5743611 polymorphism within TLR1 gene along with T/C genotype of rs3775073 polymorphism and A/G genotype of rs5743810 polymorphism within TLR6 gene were associated with a high risk of coronary artery disease (OR = 0.41 (95 % CI = 0.20-0.84), OR = 1.56, 95 % CI = 1.04-2.34, OR = 1.68, 95 % CI = 1.03-2.73, and OR = 1.55 (95 % CI = 1.12-2.14, р < 0,05, respectively) independently of age and gender. Conclusions: certain Toll-like receptor gene polymorphisms are associated with the risk of CAD.


S.V. Shishkin1, S.V. Mustafina1, S.K. Malyutina1, M. Bobak2, G.I. Simonova1, L.V. Shcherbakova1, Yu.I. Ragino1, M.I. Voevoda1
1FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Department of Epidemiology and Public Health, University College London, London, UK
Keywords: метаболический синдром, когнитивная функция, компоненты метаболического синдрома, metabolic syndrome, cognitive function, the components of the metabolic syndrome

Abstract >>
Objective: To investigate the association of metabolic syndrome (MS) and its individual components with indicators of cognitive function (CF) in a population sample of older people in Western Siberia. Material and methods . The current analysis, conducted in the frame of project supported by RSF, used the data from the international project HAPIEE which recruited a random population sample of 9.360 men and women aged 45-69 years old resident in Novosibirsk. Immediate and delayed word recall and verbal fluency tests were used to assess cognitive functions in a random subsample ( n = 4765). Metabolic syndrome was based on measurements of blood pressure, anthropometry, blood lipids and blood glucose levels. Results . After adjustment for age, sex and education, the mean immediate word recall and verbal fluence were significantly lower in subjects with MS than in persons without MS ( p < 0.05); the difference in delayed recall was not significant ( p > 0.05). Cognitive functions were significantly inversely associated with presence of all individual components of MS. Conclusion . This large study in general population of middle aged and older persons in a large industrial center of Western Siberia, we found a significant decline in cognitive functions associated with MS and its components.

Relationship of MRI pattern of carotid atherosclerotic plaque to cerebrovascular reactivity in carotid stenosIs

A.S. Maksimova, E.E. Bobrikova, M.P. Plotnikov, Yu.V. Rogovskaya, I.L. Bukhovets, M.S. Kuznetsov, W.Yu. Usov
FSBSI «Research Institute for Cardiology», 634012, Tomsk, Kievskaya str., 111a
Keywords: атеросклероз, сонные артерии, МРТ, цереброваскулярный риск, цереброваскулярный резерв, carotid atherosclerosis, сarotid arteries, MRI, stroke risk, сerebrovascular reactivity

Abstract >>
The aim of the study was to compare the structure of atherosclerotic plaques visualized using MRI with cerebral vascular reactivity detected by ultrasound in patients with carotid atherosclerosis. Materials and methods. The patients′ population comprised 21 persons (mean age 64 ± 13) with hemodynamically significant carotid artery stenosis for over 70 % of lumen. All patients underwent MR imaging of the carotid arteries. To assess the cerebrovascular reactivity transcranial ultrasound of middle cerebral artery was done and blood flow parameters were determined during the stress tests: test with breath holding and hyperventilation. Results and discussion. It was found that at test with breath holding there is a statistically significant association between MRI plaque structure and direction of the reaction ( p = 0.081), whereas at the test with hyperventilation no significant differences were found. At tests with breath holding in 56 % patients with MR images of plaque hypointense on T1-weighted scans and hyperintense on T2-weighted ones unidirectional positive response was observed; unidirectional negative response or multidirectional response were observed in patients with MR images of plaque hyperintense on T1-weighted scans and hypointense on T2-weighted ones. Conclusion. Atherosclerotic lesions of the internal carotid artery with intra-plaque hemorrhage are accompanied by critical deterioration of cerebrovascular reactivity. Thus, every hemorrhage to carotid plaque is critical risk factor and requires removal of the plaque by carotid endarterectomy. Such study may be suggested as a screening test in all patients of risk groups of atherosclerosis.


O.V. Tsygankova1, Z.G. Bondareva1, Yu.I. Ragino2, K.Yu. Nikolaev2, D.Yu. Platonov3, V.N. Maksimov2, M.G. Pustovetova1
1Novosibirsk State Medical University, 630091, Novosibirsk, Krasny av., 52
2FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
3Tver State Medical Academy, 170100, Tver, Sovetskaya str., 4
Keywords: тестостерон, эстрадиол, мужчины, лизосомальные ферменты, ишемическая болезнь сердца, estradiol, testosterone, women, coronary heart disease, lysosomal enzymes

Abstract >>
Objective: To evaluate the serum concentrations of the three markers of lysosomal hydrolases (cathepsin D, acid phosphatase (AP) and acid DNAse (aDNAase) in men with coronary heart disease (CHD), depending on the levels of testosterone (T), estradiol (E2) and age, examine their association with anthropometric, insulin-glucose parameters of lipid and non-lipid biomarkers of atherosclerosis. The study included 161 women aged 35-65 years, myocardial infarction (MI) is not less than 30 days before the survey. The median age was 53.1 years (25 % 75 % percentage: 40.1 and 59.4 years). The patients were divided into age groups: 35-55 years and 56-65 years (first and second groups, respectively), as well as in groups by levels of sex hormones: T> and ≤ 12 nmol / l and ≥ E2 and <0.194 nmol / l at twofold determination. The results of a comparative analysis and correlation in males 35-55 years of normal T and E2 levels were associated with higher serum concentrations of lysosomal enzymes than those with androdefitsitom and giperestrogeniey and at an older age, on the contrary, androdefitsit and hyperestrogenia lysosomal enzymes accompanied labilization of lysosomal enzymes. In men, CHD patients first age group according to the multivariate analysis three studied lysosomal enzyme inversely dependent on E2 ( p < 0.001) and a number of pro-atherogenic parameters including total cholesterol (TC), low density lipoprotein (LDL) cholesterol, triglycerides (TG), hip circumference (ON), body mass index (BMI), interleukin (IL) -1β ( p < 0.001-0.01), and in 56-65 years a direct impact on the levels of sex steroids lysosomal hydrolases missing, cathepsin D and EC is directly determined by the lipid, non-lipid markers of atherogenesis (TG, high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA-30), waist circumference (WC), the index of HOMA-R, p < 0.001-0.05) and back high-density lipoprotein (HDL) cholesterol ( p < 0.001). Acid DNase in both age groups dependent on the parameters involved in the insulin-glucose homeostasis (BMI, ON, TG, index HOMA-R, p < 0.001-0.05), which may reflect a key role in endonuclease accelerated catabolism activatable for various violations of carbohydrate metabolism, up to programmed cell death. Such dynamics of the three markers of lysosomal enzymes demonstrates the different contributions to the development of lysosomal cytotoxicity of CHD in men in the age groups 35-55 and 56-65 years

Features and clinical significance of inflammatory markers in patients with metabolic syndrome with and without coronary heart disease

A.A. Efremushkina1, D.M. Rudakova2, E.N. Vorobyova1
1Altai State Medical University, 656049, Barnaul, Lenin av., 40
2KGBUZ Altai Regional Clinical Hospital, 656024, Barnaul, Lyapidevskiy str., 1
Keywords: апелин, метаболический синдром, ишемическая болезнь сердца, маркеры воспаления, аpelin, metabolic syndrome, coronary heart disease, inflammation markers

Abstract >>
Aim. To study endothelial function in patients with metabolic syndrome in thepresence or absence of coronary artery disease. Material and methods. Research included 82 male patients with existence of a metabolic syndrome aged from 39 to 72 years. Patients were divided into 2 groups after verification of the diagnosis. Group 1 ( n = 40) patients without symptoms of coronary atherosclerosis made, group 2 ( n = 42) - patients with existence of a coronary atherosclerosis. Results. At patients with a metabolic syndrome and existence of an ischemic heart disease it is reliable above such markers of an inflammation bsCRP, IL-6, TFN-α, selectin and reliable there is lower than a level of cardioprotective protein of an apelin. Conclusion. Definition of early predictors of coronary heart disease can significantly influence the individual program of treatment of the patient further.


M.S. Lebedeva1,2, I.N. Grigorieva1,3, V.N. Maksimov1
1FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
2«Russian Railways» Open Joint Stock Company Railway Clinical Hospital on the Station Novosibirsk-Glavnyi, 630003, Novosibirsk, Vladimirovskiy spusk, 2a
3Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 2
Keywords: коморбидность, желчно-каменная болезнь, артериальная гипертензия, comorbidity, gallstone disease, arterial hypertension

Abstract >>
Aim. To study some features of metabolism (total cholesterol, HDL, LDL, triglycerides), blood pressure (BP), the clinical course of gallstone disease (GSD) and the quality of life (QoL) in women with GSD in combination with arterial hypertension (AH). Materials and methods. During open clinical study were examined 152 patients aged 30-60 years: 55 women with GSD and AH (group 1), 50 women with GSD without AH (group 2) and 47 women with AH without GSD (group 3). Patients of three groups were matched for age, BMI, frequency of comorbid cardiovascular diseases and diabetes mellitus type 2 ( p > 0.05). QoL was assessed by questionnaire MOS SF-36. Results. Patients of group 1 noticed pain in the right upper quadrant and dyspeptic symptoms more frequently, as compared to group 2 ( p < 0.05). Patients of group 1 showed higher values of the average sistolic blood pressure (148.4±2.6 vs. 140.1±2.8 mmHg) and diastolic blood pressure (92.0±1.3 vs. 84.9±1.5 mmHg), an increased frequency of hyper-TChol (89.1 vs. 72.3 %, p < 0.05) and hyper-LDL >3.0 mmol/l (90.9 vs. 74.5 %, p < 0.05) compared to group 3. Reducing the QoL in group 1 compared to group 3 was recorded at 4 scales and compared to group 2 - at 5 scales of 8 of questionnaire MOS SF-36 ( p < 0.05). Conclusion. Gastroenterological symptoms, lipids level and blood pressure, as well as QoL, were worse in comorbided patients with GSD and AH, compared to patients with isolated pathologies.


A.S. Asekritova, E.S. Kylbanova
Federal State Autonomous Educational Institution of Higher Professional Education, «M.K. Ammosov North-Eastern Federal University»
Keywords: артериальное давление, липиды, метаболический синдром, гастроэзофагеальная рефлюксная болезнь, blood pressure, lipids, metabolic syndrome, gastroesophageal reflux disease

Abstract >>
Lipid and metabolic risk factors for chronic noninfectious diseases for Yakuts with gastroesophageal reflux disease (GERD) and metabolic syndrome (MS) assessment work was carried out. A cross-sectional study of 140 patients with GERD was done. Depending on the MS availability and ethnicity, patients were divided into 3 groups. The main group included 50 Yakut nationality patients with GERD and MS. The comparison group I consisted of 50 Yakuts with GERD and without MS, the comparison group II consisted of 40 Russian GERD and MS. Preliminary verification of the diagnosis of GERD was done according to the Mayo Clinic and the Montreal Consensus (2006). The components of MS were determined on the basis of the recommendations of the All-Russian Scientific Society of Cardiology from 2009. Statistical processing and analysis of data was performed using the package IBM SPSS Statistics 19. Pair comparison was performed using the Mann-Whitney test. To assess the association of clinical symptoms of GERD with components of MS was used binary logistic regression method with forced inclusion of predictors. Analysis of lipid metabolic risk factors for chronic noninfectious diseases for Yakuts with gastroesophageal reflux disease and metabolic syndrome showed that sistolic and diastolic blood pressure, total cholesterol, LDL, triglycerides and the atherosclerotic index in patients with GERD and MS are characterized by high rates during normal value high density lipoprotein cholesterol. Triglyceride levels in Yakuts with MS are above recommended values, but at the same time as compared to the same period at the Russian MS were significantly lower. Assessment of the relationship of clinical symptoms of GERD with the criteria of MS in people of Yakut nationality showed the contribution of components of MS, especially abdominal obesity, high blood pressure and triglycerides, in the development of dyspeptic symptoms (bloating, heaviness in the epigastric), esophageal (epigastric burning) and extraesophageal symptoms (nocturnal cough) of GERD .

The efficacy of simultaneous action of several antisense oligonucleotide derivatives by the example of lipid metabolism in mice

S.I. Oshevskii1, Yu.I. Ragino2, E.V. Kashtanova2, Ya.V. Polonskaya2, E.M. Stakhneva2, V.P. Nikolin1, N.A. Popova1, A.N. Korablev3, N.A. Kolchanov1, M.I. Voevoda1,2,3
1The Federal Research Center Institute of Cytology and Genetics of SB RAS, 630090 Novosibirsk, Akademik Lavrent’ev av., 10
2FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
3Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 2
Keywords: антисмысловые олигонуклеотидные производные, регуляция липидного обмена, antisense oligonucleotide derivatives, lipid metabolism regulation

Abstract >>
Motivation and Aim: Demonstration of the possibility of lipid metabolism regulation by joint action of several antisense oligonucleotide derivatives (ASOs) targeted to mRNAs of closely associated proteins involved in lipid metabolism. Material and Methods: Female mice of the C57BL/6J strain; 13- and 20-mer oligonucleotide derivatives (ASOs) protected from nucleases by the presence of internucleotide thiophosphate bonds and locked nucleic acid (LNA) fragments at their 5’- and 3’- ends; conventional methods of assaying blood serum ALT, total cholesterol, TG, apolipoprotein apoB and lipoproteins: LDL-C, HDL-C. Results: Solutions of ASOs in isotonic solution were prepared in combinations: (1) anti-apoB; (2) anti-apoB + anti-PCSK9; (3) anti-apoB + anti-PCSK9 + anti-apoCIII. Four injections to the tail veins of C57BL/6J mice were done. After three injections of combination (3), done at weekly intervals, the LDL-C level decreased by 25 % with reference to the control, and the HDL-C/LDL-C ratio improved by 42 %. After subsequent injection of the ASOs accompanied by change to high-fat diet, mice exposed to combinations (2) and (3) showed lower LDL-C levels, by factors of 1.5 and 3.5 with reference to the control, and their HDL-C/LDL-C ratios were better two- and fivefold, respectively. In cases of combinations (2) and (3), a significant decrease in TG concentration was recorded, twofold in case of (3). These effects were observed at threefold fat content in the diet. The ALT level decreased significantly with transition from combination (1) to (3), i.e., when the liver experienced heavier load of oligonucleotide matter, which indicates to the absence of hepatotoxicity. Conclusions: The possibility of efficient regulatory joint action of several ASOs targeted to mRNAs of associated proteins is demonstrated by the example of lipid metabolism.


Yu.Sh. Shwartz, M.I. Chasovskikh, S.V. Cheresiz, M.V. Kruchinina
FSBSI «Institute of Internal and Preventive Medicine», 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: атеросклероз, апоптоз, эффероцитоз, внеклеточные везикулярные частицы, atherosclerosis, apoptosis, efferocytosis, extracellular vesicular particles

Abstract >>
The review summarizes current notions on the role of apoptosis and apoptotic cell-derived extracellular vesicles in atherogenesis. The mechanisms of efferocytosis impairment and its significance in atherosclerotic vulnerable plaque formation are discussed. The data on the pro- and anti-inflammatory effects of apoptotic extracellular vesicular particles are presented.

Assessment of cardio-ankle vascular index in patients with clinical manifestations of atherosclerosis

A.N. Sumin, A.V. Shcheglova
FSBSI «Scientific Research Institute for Complex Studying of Cardiovascular Diseases», 650002, Kemerovo, Sosnovyi bulvar, 6
Keywords: сердечно-лодыжечный сосудистый индекс, атеросклероз, cardio-ankle vascular index, atherosclerosis

Abstract >>
The stiffness of the arteries is an integral indicator of the state of the vascular wall, so this indicator is widely used in cardiology practice. Recently, a novel marker of arterial stiffness - cardio-ankle vascular index (СЛСИ), independent of blood pressure levels, making it more accurate and convenient for the dynamic assessment of patients. Although СЛСИ indicator is more often used in screening for and to assess cardiovascular risk, perhaps its use in patients with existing cardiovascular disease. This review focuses on the possibilities of using the СЛСИ in patients with atherosclerosis of various localization, especially in patients with stable coronary heart disease and disorders of cerebral circulation.