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The journal "Ateroskleroz"

2020 year, number 2

1.
STRUCTURE OF CALCIFICATES IN HUMAN CAROTID ARTERY ATHEROSCLEROTIC PLAQUES BY MEANS OF BACKSCATTERED SCANNING ELECTRON MICROSCOPY

R.A. Mukhamadiyarov, A.G. Kutikhin
Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy blvd., 6
Keywords: атеросклероз, атеросклеротические бляшки, кальцификация, оссификация, биоминерализация, остеохондрогенная дифференцировка, электронная микроскопия, atherosclerosis, atherosclerotic plaques, calcification, ossification, biomineralisation, osteochondrogenic differentiation, electron microscopy

Abstract >>
Aim of the study was to investigate the atherosclerotic calcification employing our original technique of tissue staining, embedding, and backscattered scanning electron microscopy. Materials and methods. Atherosclerotic plaques excised during the carotid endarterectomy have been fixed in 10 % neutral phosphate buffered saline formalin for 24 hours, stained in 2 % osmium tetroxide for 60 hours and in alcoholic uranyl acetate for 5 hours with the subsequent epoxy resin embedding, grinding, polishing, lead citrate counterstaining for 7 minutes, sputter coating with carbon and backscattered scanning electron microscopy. We then analysed localisation, structure, and microenvironment of the calcium deposits. Results. Within the atherosclerotic plaques, we identified 3 distinct calcification morphologies: compact homogenous macrocalcifications, sheet-like heterogeneous macrocalcifications along the destructed collagen and elastin fibers, and microcalcifications around large calcium deposits with the sharp margins. However, even relatively homogenous compact macrocalcifications had uneven distribution of electron density. In conjunction with groups of mineral deposits of distinct calcium phosphate phases including nascent calcified loci, this testified to ongoing calcium phosphate maturation while multiple microcalcifications merging into the single macrocalcification indicated ossification. Compact ossifying macrocalcifications with smooth margins frequently had a dense connective tissue capsule. The microenvironment of calcium deposits was often characterised by leaky neovessels. Conclusion. Diversity of calcification morphologies and ossification in atherosclerotic plaques is similar to those observed in calcific aortic valve disease and bioprosthetic heart valve failure. Combined with atherosclerotic plaque disaggregation followed by flow cytometry and single-cell RNA sequencing, our technique may improve our understanding of atherosclerotic calcification and lead to the identification of appropriate therapeutic targets to prevent or retard this process.
																								



2.
FEATURES OF LIPIDOMIC PROFILE OF ERYTHROCYTE MEMBRANES AND BLOOD SERUM IN PATIENTS WITH FATTY LIVER DISEASE

M.V. Kruchinina1, M.V. Parulikova1, S.A. Kurilovich1, A.A. Gromov1, M.V. Shashkov2, A.S. Sokolova3, V.N. Kruchinin4
1Research Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2G.K. Boreskov Institute of Catalysis of SB RAS, 630090, Novosibirsk, Academician Lavrent’ev av., 5
3N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of SB RAS, 630090, Novosibirsk, Academician Lavrent’ev av., 9
4A.V. Rzhanov Institute of Semiconductor Physics of SB RAS, 630090, Novosibirsk, Academician Lavrent’ev av., 13
Keywords: жировая болезнь печени, алкогольный, неалкогольный генез, жирные кислоты, эритроциты, сыворотка крови, диагностика, fatty liver disease, alcoholic, non-alcoholic genesis, fatty acids, red blood cells, blood serum, diagnostics

Abstract >>
The aim of the work was to study the compositional features of fatty acids of erythrocyte membranes and blood serum in patients with fatty liver disease of alcoholic (AFLD) and nonalcoholic (NAFLD) genesis for possible use for differential diagnosis. A total of 80 men (51.8±3.9 years) with AFLD ( n = 28) and NAFLD ( n = 52), as well as 20 conditionally healthy individuals were examined. The composition of erythrocyte membrane and serum fatty acids (FA) was studied using a chromatography mass spectrometry system based on three Agilent 7000B quadrupoles (USA). Differences in levels and ratios of FA in blood serum and erythrocyte membranes were revealed in patients with alcoholic and nonalcoholic fatty liver disease. Increased esterification of FA, increased synthesis of polyunsaturated (PUFA), enhancing liver damage caused by ethanol, a significant role of oleic and linoleic acids are associated with AFLD. Patients with NAFLD showed elevated levels of potentially lipotoxic saturated FA (margarine, stearic, arachinic, pentadecanoic) with a decrease in monounsaturated (palmitoleic, elaidic, oleic). A decrease in the content of docosahexaenoic n -3 PUFAs against the background of a compensatory increase in the level of docosapentaenoic FA n -6 with an omega-3 deficiency, increased consumption of omega-6 PUFAs suggest defective desaturation of unsaturated fatty acids and increased longchain PUFA peroxidation followed by oxidative stress, especially insulin resistance. The synthesis of triglycerides provides a protective mechanism against toxic accumulation of free FA in the liver. Correlation was established between the levels of FA erythrocyte phospholipids and components of the metabolic syndrome, markers of alcohol consumption. Pilot diagnostic models have been obtained that make it possible to distinguish patients with NAFLD and AFLD from healthy patients (AUC 0.892, sensitivity 0.82, specificity 0.88 for NAFLD; AUC 0.811, sensitivity 0.74, specificity 0.80 for ASFLD), as well as NAFLD from AFLD (AUC 0.790, sensitivity 0.73, specificity 0.78). FA profiles of erythrocyte membranes and blood serum are reliable biomarkers of disorders in lipid metabolism in patients with fatty liver disease of various genesis and are promising from the point of view of differential diagnosis.
																								



3.
ASSOCIATIONS OF EPICARDIAL FAT THICKNESS AND CIRCULATING MARKERS OF MYOCARDIAL FIBROSIS IN PATIENTS WITH MYOCARDIAL INFARCTION

E.V. Belik, O.V. Gruzdeva, Yu.A. Dileva, D.A. Borodkina, N.K. Brel, E.E. Bychkova, T.B. Pecherina, V.N. Karetnikova, V.V. Kashtalap, E.I. Palicheva, A.A. Kuzmina, E.V. Fanaskova, O.L. Barbarash
Research Institute for Complex Issues of Cardiovascular Disease, 650002, Kemerovo, Sosnovyi bulvar, 6
Keywords: эпикардиальная жировая ткань, фиброз миокарда, циркулирующие маркеры фиброза миокарда, висцеральное ожирение, epicardial adipose tissue, myocardial fibrosis, circulating markers of myocardial fibrosis, visceral obesity

Abstract >>
Aim: to determine the association of the thickness of epicardial adipose tissue (EAT) with the level of biological markers and the degree of myocardial fibrosis one year after myocardial infarction (MI) in patients with visceral obesity (VO). Materials and methods: the study included 88 patients with MI who were then divided into 2 groups: with and without it. VO and myocardial fibrosis a year after MI were measured by magnetic resistance tomography (MRI). Serum levels of COL 1, PICP, PIIINP on the 1st day of MI and after 1 year were determined by enzyme-linked immunosorbent assay (ELISA). The results were analyzed using Statistica 6.1 and SPSS 17.0 for Windows. Results: in the presence of VO, an increase in the thickness of EАT, development of cardiofibrosis after 1 year, and an increase in circulating markers of fibrosis in the acute period of MI were observed. A direct correlation was found between the thickness of EАT and the concentration of markers of myocardial fibrosis both on the 1st day of MI and after a year, as well as the percentage of cardiofibrosis and COL1, PICP, PIIINP, on the 1st day of MI for both groups, one year after MI this relationship persisted only in individuals with VO ( r = 0.54, p = 0.01; r = 0.33, p = 0.00; r = 0.51, p = 0.01). Conclusions: the fact of VO in patients with MI is associated both with an increase in the thickness of ECT, the development of cardiofibrosis one year after MI, and with an increase in serum levels of COL 1, PICP and PIIINP on the 1st day and a year after the MI. In addition, the thickness of EАT is directly proportional to the degree of VO, and the levels of myocardial fibrosis markers depend on the value of EАT, this makes it possible to consider EАT as an additional indicator of myocardial fibrosis
																								



4.
ASSOCIATIONS OF OVERWEIGHT AND POLYPHENOLS CONSUMPTION IN THE POPULATION OF HIGH CARDIOVASCULAR RISK

T.I. Batluk, D.V. Denisova, I.P. Berezovikova, S.K. Malyutina
Research Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: полифенольные соединения, избыточная масса тела, популяция, polyphenols, overweight, population

Abstract >>
Aim of the study was to identify associations of polyphenolic compounds consumption in general and their individual classes with excess body weight in the population of Novosibirsk. Material and methods. In 2003-2005, in the frames of the HAPIEE international project «Determinants of cardiovascular diseases in Eastern Europe: a multicenter cohort study» the population sample aged 45-69 (9360 people, 4266 men and 5094 women, average age - 57.6 years) was examined in Novosibirsk. The calculation of body mass index (BMI) was carried out according to the formula: BMI (kg / m2) = weight (kg) / height2 (m2). The BMI classification of obesity was used (WHO, 1997). For the analysis of nutrition, we used a semi-quantitative frequency questionnaire - Food Frequency Questionnaire (FFQ) and the European database Phenol-Explorer 3.6. Results. The chance of developing overweight in women decreases by 24% with high polyphenols consumption in general: odds ratio (OR) 1.24 (confidence interval (CI) 1.01-1.53), p = 0.048. For a high consumption of phenolic acids in the whole population, the probability decreases by 26 %: OR 1.26 (CI 1.11-1.44), p < 0.001; in women - by 57 %: OR 1.57 (CI 1.27-1.94), p < 0.001. In a population, the probability of developing overweight with a high consumption of stilbenes decreases by 21 %: OS 1.21 (CI 1.06-1.4), p = 0.004, in women - by 37 %: OS 1.37 (CI 1,11-1.7), p = 0.003; for the class of other polyphenols, the chance decreased in the population by 30 %: OR 1.3 (CI 1.13-1.46), p = 0.001, in women by 50 %: OR 1.5 (CI 1.22-1.84 ), p < 0.001. Conclusions. High levels of polyphenols consumption in general, as well as phenolic acids, stilbenes, and the class of other polyphenols reduced the chance of overweight developing.
																								



5.
PATHOLOGICAL CHANGES OF THE EYE RETINA AT CARDIOVASCULAR DISEASE AND DIABETES MELLITUS

A.O. Direev1,2, I.V. Munts1, O.N. Kuleshova1, E.V. Mazdorova2, A.N. Ryabikov1,2, S.K. Malyutina1,2
1Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasnyy av., 52
2Research Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: сетчатка глаза, глазное дно, атеросклероз, нейропатия, глазной ишемический синдром, окклюзия центральной артерии сетчатки, диабетическая ретинопатия, сердечно-сосудистые заболевания, артериальная гипертензия, eye retina, fundus, atherosclerosis, neuropathy, eye ischemic syndrome, central retinal artery occlusion, diabetic retinopathy, cardiovascular diseases, arterial hypertension

Abstract >>
Objective. In this work we analyzed the current literature data about the retinal damage in cardiovascular diseases and diabetes mellitus (published from 2005 to 2020). The damage of retinal vascular bed and optic nerve represents a relevant problem in the modern world in view of the significant prevalence, severity of retinal irreversible damage leading to disability, and in relation to comorbidity with cardiovascular diseases (CVD). Methods. Publications on selected topic were analyzed from 2005 to 2020. The search was carried out using the electronic databases of the Google Academy (https://scholar.google.com/), PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), eLIBRARY.ru (https: //www.elibrary.ru/) and foreign and national journals devoted to cardiology, therapy and ophthalmology. Results. The analysis of literature showed that atherosclerotic lesion of the microvascular retinal bed is a significant risk factor for acute coronary syndrome myocardial infarction (MI) and stroke. However, the identity of atherosclerotic processes occurring in the retinal vascular bed and in the peripheral arteries remains open. A strong association was shown between hypertensive retinopathy (HR) has with MI, congestive heart failure (CHF) and CHD mortality in large-scale population-based studies such as ARIC and Rotterdam Study. The question of the predictive significance of GR, depending on its degree, remains debatable. There are consistent evidence on the association between HR and CHD and CHF. Diabetic retinopathy (DR) represents a neurovascular complication of diabetes. In predominantly clinical work, there is evidence of the significance of DR as a risk marker for Stroke, diabetics peripheral neuropathy, autonomic cardiac neuropathy, thickness of carotid intima-media, micro albuminuria. A number of other major clinical works has not shown a significant association between DR and stroke. A significant drawback of investigation of the relationship between DR and CVD is a lack of population studies on this topic. Conclusions. Despite the use of modern diagnostic methods and a fairly large number of studies of the eye vascular bed and retina, the data about their relationship with CVD remain scare and contradictory, which is largely due to the limited size of the studied samples, the variability of the estimates, and a complexity of the pathway of atherosclerosis and CVD. The study of association between CVD and retinal pathology in the Russian population with using of automatic assessment of the microvascular bed provides a unique opportunity to solve some contradictory aspects and obtain new data.
																								



6.
PERIVASCULAR ADIPOSE TISSUE AND ATHEROSCLEROSIS: PHENOTYPIC FEATURES AND THERAPEUTIC POTENTIAL

D.A. Borodkina, O.V. Gruzdeva, E.V. Belik, Yu.A. Dyleva, E.I. Palicheva
Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy blvd., 6
Keywords: периваскулярная жировая ткань, белая жировая ткань, воспаление, сердечно-сосудистые заболевания, perivascular adipose tissue, white adipose tissue, inflammation, cardiovascular disease

Abstract >>
This review is devoted to the analysis of data on the study of the endocrine function of perivascular adipose tissue (PVAT), its role in the synthesis and secretion of adipocyte hormones - adipokines (leptin, adiponectin, resistin). The results of studies on the possible systemic and local effects of PVAT are reflected. Demonstrated data on the phenotypic affiliation of PVAT, the features of its endocrine and paracrine functions. Pro-and anti-inflammatory agents secreted by PVAT affect vascular health and are involved in the pathogenetic mechanisms of the development of atherosclerosis. This review summarizes current evidence that PVAT refers to special types of adipose tissue, in terms of both functionality, origin, and role in the development of cardiovascular diseases caused by obesity. In general, PVAT can be considered as a promising pharmacological target for the prevention of cardiovascular risks associated with these diseases.
																								



7.
COVID-19 AND CARDIOVASCULAR DISEASES

Ya.V. Polonskaya, E.V. Kashtanova, E.M. Stakhneva, E.V. Sadowski, Yu.I. Ragino
Research Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: сердечно-сосудистые заболевания, COVID-19, коронавирус, cardiovascular diseases, COVID 19, coronavirus

Abstract >>
At the beginning of June 2020, more than 7 million people were identified worldwide with COVID-19, a new coronavirus infection that has spread around the world, more than 400 thousand people have died. In Russia, the number of cases exceeded 470 000 people, and more than 5900 died [https://covid19-2020.info/] More and more researchers report a greater likelihood of infection and adverse disease course in people with cardiovascular diseases, which makes it necessary to study the effect of SARS-CoV-2 on the cardiovascular system. This article provides an analysis of the publications for the year 2020 from the databases of PubMed, Google Scholar, and E-library on this issue.