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2014 year, number 3

1.
FORMATION OF MACROPHAGE PHENOTUPE IN INFLAMMATORY AND FIBROGENIC RESPONSE: THE ROLE OF MEVALONATE PATHWAY AND NUCLEAR RECEPTORS LXR

Ya.Sh. Shvarts, M.I. Chasovskikh, O.M. Dolganova
Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: inflammation, fibrosis, macrophages, cytokines, cholesterol, oxysterols, mevalonate pathway

Abstract >>
Free cholesterol (Ch) and its oxidative derivatives, oxysterols (OS), are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and OS on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. Both Ch and OS are able to affect mevalonate pathway activity and activity of nuclear hormonal receptors LXR. However the roles of LXR and mevalonate pathway in Ch and OS effects on macrophage polarization are unknown. We studied the effects of Ch, OS, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10 and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 g/mL), 25-hydroxycholesterol (25-OH-Ch) (5 g/mL), 7-keto-Ch (5 g/mL), farnesol (10 M), or atorvastatin (5 mol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS-stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that the presence of Ch in microenvironment of inflammatory macrophages promotes anti-inflammatory and fibrogenic macrophage response; the latter is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol. At the same time hydroxysterols suppress both pro- and anti-inflammatory macrophage response independently of the impact of these compounds on mevalonate pathway. Apparently, pharmacological interference in the process of farnesylation could be a new approach to the control of chronic inflammation, including atherogenesis.



2.
CONTRAST-ENHANCED MRI IMAGING OF ATHEROSCLEROTIC LESIONS OF THE AORTIC WALL

A.S. Maksimova, V.E. Babokin, I.L. Bukhovets, E.E. Bobrikova, Yu. V. Rogovskaya, P.I. Lukyanenok, V.Yu. Usov
Research Insitute of Cardiology of SB RAMS, 634012, Tomsk, Kievskaya str., 111-a
Keywords: atherosclerosis of aorta, MRI, contrast-enhanced imaging of plaques, chest MRI

Abstract >>
Aim of the study. To analyze MR tomographic imaging features of atherosclerotic lesions of the aorta, with a paramagnetic contrast enhancement, in patients with extensive atherosclerosis and old acute myocardial infarction (AMI). Material and methods. The patients population comprised 33 patients with multiple atherosclerosis and old transmural AMI of the left ventricle. As control group eight patients with tumor pathology of the thorax were employed, without evidence of clinically significant atherosclerosis of the same age range. All patients underwent contrast-enhanced study (paramagnetic in standard dose of 0.1 mmol / kg BW) and index of enhancement (IE) of T1-weighted images was calculated as the ratio of intensities over the aortic wall on contrast and initial MRI studies. Geometric diameter and wall thickness of the aorta at the level of accumulation of contrast-paramagnetic material were also determined. Results and discussion. In 25 (76 %) patients with extensive atherosclerosis and old AMI IE of the atherosclerotic lesions in the aortic wall in all cases was over 1.14 (mean 1.17 0.13), far more than increasing of intensity in the control group. In eight patients (24 %) the lack of accumulation of contrast-paramagnetic material in the aortic wall was noted. Types of accumulation of contrast paramagnetic was assigned as a local or diffuse accumulation syndrome, depending on the length and circularity of the lesions. A local syndrome of accumulation was found in 15 patients, with IE = = 1.09 0.06, aortic diameter and wall thickness at the level of accumulation of contrast equal to 2.66 0.35 cm and 0.5 0.13 cm, respectively. Diffuse type of accumulation was found in 10 patients in this case IE = 1.26 0.13 aortic diameter and the wall thickness at the accumulation of contrast are 2.4 0.34 cm and 0.53 0.11 cm, respectively. In the control group no significant accumulation of contrast paramagnetic material in the aortic wall was observed, IE did not exceed 1.04 (mean 1.01 0.02). Conclusion. Contrast-enhanced MRI allows to visually and quantitatively assess pathology of aortic wall in atherosclerosis.



3.
THE STRUCTURAL CHARACTERISTICS OF THE WALL OF CAROTID ARTERIES IN OLDER WOMEN AND THEIR PROSPECTIVE DETERMINANTS IN THE POPULATION

S.K. Malyutina1,2, Yu.Yu. Palekhina2, A.N. Ryabikov1,2, S.G. Shakhmatov1,2, M. Bobak3
1Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
3University College London, United Kingdom, London, 1-19 Torrington Place
Keywords: intima-media, atherosclerosis, carotid arteries, women, population, risk factors, cardiovascular disease

Abstract >>
Purpose: To study the age gradient and prospective determinants of the structural characteristics of the arterial wall in the Novosibirsk population of older women (in the cross-sectional and prospective analysis). Methods and data source: Random population sample (338 women, 52-79 years) was examined with ultrasound of the carotid arteries (CA) and repeated epidemiological evaluation of CVD and risk factors. The materials of baseline survey performed at age of 45-69 years were used. The average follow-up period was of 8.5 years. We analyzed age gradient of carotid intima-media thickness (CIMT) and carotid atherosclerotic plaques (P) and their association with risk factors in cross-sectional and prospective design. Results: The mean maximum CIMT was ( M SE ) 0.79 0.01mm (75 = 0.89 mm), the frequency of CP - 54.2 %. CIMT increased by 0.06-0.07 mm by age decade, frequency CP increased from 31 % to 73 % in women aged 52-79 years old. In cross-sectional analysis CIMT was positively associated with age, SBP, history of diabetes with treatment. Prospective predictors CIMT were: age SBP and menopause, measured at age 45-69 years old. In cross-sectional analysis CP was positively associated with age, SBP, smoking, presence of CVD and negatively associated with alcohol intake. Prospective predictors of CP were age, SBP, LDL cholesterol and smoking, measured at age 45-69 years old. Conclusion: In female Siberian population aged 52-79 the reference value of CIMT was 0.89 mm (corresponding to established criteria 0.90 mm). Age gradient of CIMT increase and CP frequency were calculated. The determinants of CIMT were age, systolic blood pressure, diabetes with treatment history (in older age) and the menopause (in middle age). The presence of CP were determined by age, systolic blood pressure, LDL cholesterol, and smoking (in middle and older age), and it was negative associated with alcohol intake and positively - with history of CVD (in older age). The study results can be used to improve prevention of atherosclerosis in women.



4.
APPLICATION OF BIOLOGICAL MARKERS OF KIDNEY INJURY FOR PROGNOSIS OF LONG-TERM ADVERSE OUTCOMES IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

O.L. Barbarash1,2, I.S. Bykova1, V.V. Kashtalap1,2, M.V. Zykov1, O.N. Khryachkova1, V.V. Kalaeva1, K.S. Shafranskaya1, V.N. Karetnikova1,2
1Research Institute for Complex Issues of Cardiovascular Diseases SB RAMS, 650002, Kemerovo, Sosnovy Blvd., 6
2Kemerovo State Medical Academy of Minzdrav of Russia, 650039, Kemerovo, Voroshilov str., 22A
Keywords: NGAL, myocardial infarction, renal dysfunction, prognosis, NGAL

Abstract >>
Objective: To study the prognostic significance of serum NGAL (sNGAL) and cystatin C in the acute phase of ST-segment elevation myocardial infarction (STEMI) in the late disease period. Material and Methods: 357 patients with STEMI, admitted to hospital within 24 h of symptom onset, were included in the study. Serum creatinine levels with the calculation of glomerular filtration rate (GFR) using the MDRD as well as levels of sNGAL and cystatin C were measured on day 1 and 12-14. Results: All patients were divided into 2 groups according to their estimated GFR: with and without renal dysfunction (RD), defined as a decrease of GFR < 60 ml/min/1.73 m 2. Within 3 years of follow-up, the composite endpoint (CEP) were assessed (CEP - death + non-fatal cardiovascular events). The ROC curve analysis was used to determine the thresholds for every biomarker, involved in the CEP development: NGAL (≥ 1.25 ng / ml) and cystatin C (≥ 1.9 mg / l). On day 12-14 of hospitalization elevated NGAL ≥ 1.25 ng / mL was associated with a 3-fold increased risk for adverse cardiovascular events in a 3-year follow up after STEMI; whereas, elevated cystatin C ≥ 1.9 mg/l - with a 2-fold increased risk for the CEP, and signs of RD, found in patients before the discharge from the hospital, - with a 1.5-fold increased cardiovascular risk. The model considering an increase of NGAL over 1.25 ng / l has the highest prognostic value, while the models based on the levels of cystatin C and GFR are of equal prognostic value. Conclusion: The most promising issue in the prognosis of long-term adverse outcomes in patients with STEMI may be considered the assessment of RD using new biomarkers such as sNGAL.



5.
LIPID PROFILE IN YOUNG PATIENTS WITH DIABETES MELLITUS

A.K. Ovsyannikova, O.D. Rymar, M.I. Voevoda
Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: diabetes mellitus, lipid profil, young patients

Abstract >>
Diabetes mellitus (DM) is refered to the socially significant diseases. It is characterized by a high percentage of violations of disability in young adults and the high percentage of disability, mortality in other age groups. Dyslipidemia presents in all age groups in patients with diabetes, which is why in these patients is necessary to determine the lipid profile. In 70 patients with onset type 1 diabetes, type 2 and MODY 2 under the age of 25 years were determined lipid profile: total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Statistically significant differences were not received at one indicator of lipid profile between patients with type 1 diabetes, type 2 diabetes and MODY 2.



6.
FEATURES OF THE LIPID PROFILE OF BLOOD IN WOMEN OF PRE-RETIREMENT AND RETIREMENT AGE

Yu.P. Nikitin, S.K. Malyutina, K.V. Makarenkova, L.V. Shcherbakova
Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: blood lipids, women age

Abstract >>
Objective: To analyze the possible features of the blood lipid parameters of women in pre-retirement and retirement age. Materials and methods. We used materials of the two major international projects - «MONICA and «HAPIEE. According to the protocol of these projects a representative sample of the Novosibirsk population have been surveyed. The analysis included data of 6092 women aged 45-64 years. Results. Levels of TC, nonHDL, LDL in women aged 45-54 years were slightly lower (an average - 10 %) than in the 55-64 years, but the frequency of hypercholesterolemia of LDL was high. Similar characteristics were obtained for the values of the so-called «atherogenic coefficient. Conclusion. «Pro-atherogenic potential of blood lipid profile in women in pre-retirement and the retirement age is significant. In this connection, it is advisable to wider use lipid-lowering medicaments for women 45-54 years in order to reduce the risk of cardiovascular morbidity and mortality.



7.
ROLE AND OPPORTUNITIES FOR HEALTH CENTER IN CORRECTION OF RISK FACTORS OF CARDIOVASCULAR DISEASE (CASE STUDY POPULATION provision of advice to stop smoking)

N.E. Naydenova1, E.N. Lobykina2
1Tomsk regional clinical hospital, 634063, Tomsk, I. Chernykh str., 96
2Novokuznetsk State Institute of Postgraduate Medicine, 654005, Novokuznetsk, Stroiteley av., 5
Keywords: cardiovascular disease, risk factors, smoking, counseling, smoking cessation

Abstract >>
The purpose of the study - analysis of advice to the adult population smoking cessation in the health center to assess the effectiveness of counseling system «Treatment of the smoker. Materials and methods. Advice on smoking cessation in the department of «Health Center Tomsk regional clinical hospital is organized in the form of individual and group counseling. Vykipirovka data from medical records of the adult population aged 18-86 years, held in 2012 and 2013 in the (H) was conducted. All persons handling smokers conducted baseline survey, measurement of carbon monoxide in exhaled air analyzer Micro CO, assessment of the level of nicotine dependence (test Fagerstrema) and questionnaires to determine readiness to quit smoking. Since November 2013 conducted testing using computer consulting system «Treatment smoker («Research Institute of Pulmonology FMBA of Russia). Vykipirovka data from the counseling system «Treatment smoker smoking 98 persons who applied to (HC) from November 2013 to March 2014 was carried out. Results. The prevalence of smoking among men and women attending (HC) Tomsk, GFR was significantly less than nationwide data. Smoking middle-aged women are more likely than male smokers to seek help in quitting smoking. As a result, group and individual counseling during the study period had quit smoking 10 % of women and 18 % men. 16 % of women and 21 % men reduced the intensity of smoking. 74 % of women and 61 % continue to smoke. Conclusion. Organization of medical care for smoking cessation in primary care is an extremely promising avenue for prevention and treatment of cardiovascular diseases. Individual counseling with computer-based testing «Treatment smoker is available form of obtaining preventive advice for people wanting to quit smoking. Using the (CS) improves the quality of care: allows you to automate the entire process of diagnosis smoking status, including determining the type of smoking behavior and smoker index, automates the process of drawing up programs for smoking cessation.



8.
THE STUDY OF ASSOCIATION BETWEEN LIPID FRACTIONS LEVELS AND IMMEDIATE AND DELAYED REPRODUCTION OF VERBAL INFORMATION

A.V. Sukhanov, D.V. Denisova, Yu.I. Ragino
Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: test Luria, cognitive function, serum lipids

Abstract >>
Background: The literature data about the association between disorders of immediate and delayed reproduction of the verbal information with lipid levels in young and middle age at the present time remains controversial. Objective: To examine the association of different levels of lipid fractions with direct and delayed recall of words in the A.R. Luria test at the each five-year period in both sexes aged 25-45. Methods: The study involved 536 people aged 25 to 45 years - Novosibirsk residents of both sexes. The concentration of serum lipid levels were measured by enzymatic method. Immediate and delayed reproduction of words was assessed using the technique of memorizing 10 words, proposed A.R. Luria. Analysis of the material was carried out using the methods of descriptive statistics, correlation analysis and multiple linear regression in the statistical package «R for Windows. Results: The levels of total cholesterol showed a weak positive correlation with the number of words with delayed reproduction in Luria test that found its confirmation when performing regression analysis. At the same time, the triglyceride levels negatively correlated with the average number of correctly named words with direct playback, which is also confirmed by multiple linear regression. Conclusion: Association of lipid profile and the assessment of cognitive functions fails to recognize at a young age. Analysis of the associations in the future may be of great interest for the detailed development of the theory of memory.



9.
SMOKING AND ITS ASSOCIATION WITH SOCIO-ECONOMIC AND CARDIOMETABOLIC RISK FACTORS IN THE POPULATION 25-45 YEARS OF NOVOSIBIRSK. THE PROBLEM OF FEMALE SMOKING (2013-2014)

D.V. Denisova, N.A. Kovalkova, E.V. Kashtanova, Ya.V. Polonskaya, L.V. Shcherbakova
Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: smoking, population, socio-economic factors, cardiometabolic factors, serum cotinine

Abstract >>
The article presents the results of population-based study of a representative sample of the population of one of the districts of Novosibirsk, conducted in 2013-2014. A total of 749 people of both sexes (43 % men) aged 25-45 years were examined. The response rate was 38 %. The program included a survey questionnaire on smoking and socio-economic factors (education, marital status, employment). Measurement of blood pressure, anthropometric parameters, serum cotinine, total cholesterol and its fractions, blood glucose were conducted. The high prevalence of smoking among men (46 %) and women (24 %) revealed. Associations of smoking with cardiometabolic risk factors such as hypertension, hyperglycemia and hypo-HDL-C were received. On the subsample (273 people) using the verification of the questionnaire on smoking by serum cotinine 4-6 % false answers were found. Marked increasing in female smoking and decreasing in male smoking in the past 20 years in Novosibirsk were revealed.



10.
ERYTHROCYTES AND NO: THE FACTS AND HYPOTHESES INTERACTION, PROSPECTS FOR DIAGNOSIS AND THERAPY

M.V. Kruchinina1, A.A. Gromov1, I.O. Svetlova1, V.M. Generalov2, A.S. Safatov2, G.A. Buryak2, V.N. Kruchinin3, S.V. Rykhlitsky3
1Research Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2State Research Center of Virology and Biotechnology Vektor, 633159, Novosibirsk region, Koltsovo
3Institute of Semicontuctor Physics named after A.V. Rzhanov, 630090, Novosibirsk, Akademic Lavrentev av., 13
Keywords: red blood cells, nitric oxide, adenosine triphosphate, endothelial cells, vasoregulation, deformability, the bioavailability of NO, Raman-spectroscopy

Abstract >>
This review deals with the relationship between red blood cells and nitric oxide, the role of erythrocytes as participants of vasoregulation. There were the results of studies on the physiological origin of vasoactive NO under hypoxic conditions, sources of nitric oxide associated with erythrocytes. The data of the NO effect on the erythrocyte deformability have been analyzed. The hypothesis of insufficient NO bioavailability during blood storage caused by degenerative changes in red blood cells (increased levels of free hemoglobin and microparticles from erythrocytes) was presented. The results of evaluation of hemoglobin associated with NO by means of Raman-spectroscopy were given. Prospects have been identified in the diagnosis and therapy related to the definition and changes in levels of erythrocyte-derived NO and ATP.