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The journal "Ateroskleroz"

2017 year, number 2

1.
Contact ROS1, TAS2R50, ZNF627, MIAF3 genes and 16q23.1, 6p24, 9p21 chromosomal regions with myocardial infarction in Caucasians of Novosibirsk in two age groups

P.S. Orlov1,2, N.G. Lozhkina3, V.N. Maksimov1,2, A.D. Kuimov3, S.K. Malyutina1, M.I. Voevoda1,2
1Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2National Research Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 2
3Novosibirsk State Medical University, 630091, Novosibirsk, Krasny av., 52
Keywords: myocardial infarction, SNP, rs1333049, rs4804611

Abstract >>
Aim: Investigate relations of 8 SNPs with myocardial infarction in groups of up to 55 years and after 55 years. Methods: The group of patients with myocardial infarction, arrived in the intensive care unit City Clinical Hospital 1 (2009-2010 gg.) 160 people (113 men and 47 women). The control group was formed based on the sample of population 45-69 year old residents of the October and the Kirov district of Novosibirsk (9.400 people), which was collected by Institute of Internal Medicine SB RAMS during the work on the international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). It included 420 people with no signs of myocardial infarction (men 270, women 150). Genomic DNA was isolated from venous blood by phenol-chloroform extraction. SNP of gene were tested by RT-PCR according to the protocol of the manufacturer (TaqMan Probes, Applied Biosystems, USA) on the device ABI 7900HT. In a study following SNPs were taken: rs499818, rs619203, rs1333049, rs1376251, rs2549513, rs4804611, rs17465637. Results: For rs1333049 were shown an association with MI: SS OR = 2.05 (95 % CI 1.35-3.12 p = 0.001, CC vs CT + TT) and PT OR = 0.59 (95 % CI 0.37-0.93; p = 0.023; CT vs CC + TT) in the group. In both age groups, an association has been confirmed: SS OR = 2.92 (95 % CI 1.39-6.16; p = 0.006; CC vs CT + TT) for junior and SS OR = 1.77 (95 % CI 1.05-2.97; p = 0.035; CC vs CT + TT) and senior groups. For rs4804611 shows a predisposing role in relation to MI AA OR = 1.63 (95 % CI, 1.03-2.45; P = 0.04; AA vs AG + GG) in the older age group, for the remaining SNPs statistically valid data has been received. Conclusions: Thus in this study were confirmed by rs1333049 association (hr. 9) with myocardial infarction, regardless of age, as well as shows the association of rs4804611 in the group over 55 years.



2.
AN ANTISENSE OLIGONUCLEOTIDE DERIVATIVE TO THE MRNA OF THE NAV1.5 SODIUM CHANNEL GENE (SCN5A) DECREASES THE HEART RATE

S.I. Oshevskii1, Yu.I. Ragino2, E.V. Kashtanova2, Yu.V. Polonskaya2, E.M. Stakhneva2, V.P. Nikolin1, N.A. Popova1,3, N.A. Kolchanov1, M.I. Voevoda1,2,3
1The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Academician Lavrentev av., 10
2Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
3National Reseach Novosibirsk State University, 630090, Novosibirsk, Pirogov str., 2
Keywords: antisense oligonucleotide derivative, SCN5A gene, C57BL/6J mice, heart rate

Abstract >>
Objective: To assess the potential of a new approach to altering the heart rate by expression inhibition of the SCN5A gene, encoding a classical sodium channel, Nav1.5, with an antisense oligonucleotide derivative in the case study of the mouse. Material and methods: C57BL/6J male mice; oligonucleotide derivative with a length of 15 nucleotides protected from nucleases by the presence of internucleotide phosphorothioate bonds and LNA (locked nucleic acids) blocks at the 5ʹ and 3ʹ ends (ASO); standard injection of ASO in physiological saline solution into the mouse caudal vein; standard technique for determination of the heart rate and blood pressure in mice with a CODA Surgical Monitor (Kent Scientific, United States); and standard quantification of apoB apolipoprotein and lipoproteins HDL-C, LDL-C, total cholesterol, TG, and ALT in the blood serum. Results: ASO decreases the heart rate in mice by 12 % over 10 days and further uniformly accelerates the heart rate to almost initial level by day 16 as well as gently decreases the mean values of systolic and diastolic pressures with their subsequent increase and gradual redistribution of excess pressure in the control and experimental animal groups. The level of lipid metabolism in experimental animals is decreased. Conclusions: The new approach to alter the heart rate by inhibition of the SCN5A gene expression with an antisense oligonucleotide derivative is shown to be feasible. The impact is accompanied by minor changes in the systolic and diastolic pressures and a decrease in the level of lipid metabolism. The preparation is promising in terms of the influence on the heart rate taking into account the further insight into its effect at different concentrations and possible insignificant side effects.



3.
FOR INVESTIGATING BIOCHEMICAL MARKERS OF PROGNOSIS OF MYOCARDIAL INFARCTION

R.I. Vorobev1, E.A. Sharlaeva2, E.N. Vorobeva3, G.G. Sokolova2
1Regional Clinical Hospital of Emergency Medical Care, 656049, Altai Krai, Barnaul, Peschanaya str., 89-270
2Altai State University, 656049, Barnaul, Lenin av., 61
3Altai State Medical University of Minzdrav of Russia, 656049, Barnaul, Peschanaya str., 89-270
Keywords: cardiovascular diseases, myocardial infarction, biochemical markers of cardiovascular diseases, A1 apolipoprotein, apolipoprotein B, relation Apo B /Apo1

Abstract >>
The mortality from cardiovascular disease in Russia remains high. The target of the real work was the research of new biochemical markers of ardiovascular diseases and their probable complications (an apolipoprotein of A1 (Apoa1), an apolipoprotein B (ApoB), relation ApoB/ApoA1) at residents of Altai region. It is shown that between men and women statistically significant distinctions are revealed on all analyzed markers of possible complications: contents ApoB, coefficient of ApoB/ApoA1 at men is higher, and the contents ApoA1 - is below, than at women.



4.
MYOCARDIAL INFARCTION, STROKE: GENDER DIFFERENCES, DEVELOPMENTAL RISK AND PERSONAL ANXIETY AMONG THE POPULATION IN RUSSIA/SIBERIA (WHO PROGRAM MONICA-PSYCHOSOCIAL)

V.V. Gafarov1,2, E.A. Gromova1,2, D.O. Panov1,2, I.V. Gagulin1,2, A.V. Gafarova1,2
1Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Collaborative Laboratory of Cardiovascular Diseases Epidemiology
Keywords: risk, differences, high level of anxiety, population, myocardial infarction, stroke

Abstract >>
Objective: o determine the effect of a high level of personal anxiety on the difference in the risk of myocardial infarction (HR) and stroke in men and women in an open population of 25-64 years in Novosibirsk. Material and methods: A random representative sample of the population aged 25-64 years of Novosibirsk in 1994 (men n = 657, women n = 870) was examined in the framework of the III screening of the WHO MONICA-psychosocial program. The program included: registration of socio - demographic data, identification of personal anxiety (LT). Over a 16-year period, new cases of myocardial infarction (MI) and stroke were in women 15 and 35 cases; In men 30 and 22 cases, respectively. The statistical analysis was carried out using the SPSS version 11.5 software package. The criterion χ2 was used, for the development risk assessment (HR) - Cox-regression model (Cox-regression). Reliability in all types of analysis was adopted at a significance level of p ≤ 0,05. Results: In an open population of 25-64 years, VUT was defined in 59.9 % of women and 50.9 % of men. In the Cox single-factor model, after 16 years, HRM in persons with VUT was higher among women than among men (HR = 4.19 and HR = 3.7, respectively), and stroke was higher in men than in women (HR = 4.43 and HR = 3.5, respectively). In the multifactorial model of Cox in 55-64-year-old people, the influence of VUT on HRM was preserved, which was higher in women than in men (HR = 5.95, HR = 3.56, respectively). The greatest HR stroke, in the presence of VUT, was in divorced (HR = 5,017) and widowed men (HR = 3,848), aged 55-64 years (HR = 5,8). Among women, such patterns were not revealed. Conclusion: The prevalence of VUT among the population is more than 50 % and higher in women than in men . The risk of MI development over a 16-year period was higher in women, and in stroke in men.



5.
MOLECULAR-GENETICAL MARKERS OF LIPID ABNORMALITIES AND SUDDEN CARDIAC DEATH

A.A. Ivanova
Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: sudden cardiac death, single nucleotide polymorphism, APOE, LIPC, SREBF2, USF1, CETP, USF1, LDLR

Abstract >>
Sudden cardiac death is one of main problem of modern medicine. Sudden cardiac death is about 50 % of all cardiac deaths. The main part of people who died of sudden cardiac death didnt have any cardiac illnesses. In the world molecular genetic markers of sudden cardiac death are studied to create an effective system of diagnostic of predisposition and prophylactic of sudden deaths, especially to people without cardiac diseases. Lipid abnormalities are one of risk factor of sudden cardiac death. Single nucleotide polymorphisms of CETP, APOE, SREBF2, SCAP, LIPC, USF1, LDLR genes were studied as molecular genetic markers of sudden cardiac death.



6.
LEFT VENTRICULAR STRAIN: SEX- AND AGE-RELATED CHARACTERISTICS AND ASSOCIATIONS WITH CARDIOVASCULAR DISEASES (REVIEW OF LITERATURE)

V.P. Guseva1, S.K. Malyutina1,2, A.N. Ryabikov1,2, E.V. Voronina1, E.V. Shubkina1, A.I. Sinyova2
1Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Novosibirsk State Medical University, 630091, Novosibirsk, Krasny av., 52
Keywords: myocardial strain, strain rate, speckle tracking imaging, risk factors, cardiovascular disease, prognosis

Abstract >>
The standard indicators of function of the left ventricle (LV) (ejection fraction, end-diastolic and end-systolic volumes, of local contractility) depend on the circulation load and partly are subjective. The indices of myocardial deformation allow to objectify the assessment of left ventricular function and to detect changes even in subclinical myocardial lesion. Objectives. This review analyzes the literature data focused on the ultrasound assessment of myocardial deformation (Strain) in various cardiovascular diseases (CVD), published during the last 15 years (2001-2016) using PubMed (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar (https://scholar.google.ru). Results. The deformation of LV myocardium, as a 3D object, is considered as a longitudinal, circular and radial Strain. According to data obtained, the indicators of myocardial Strain are related to age and sex (in men lower than in women, decreased with aging), they have diagnostic significance for myocardial infarction, acute and chronic heart failure (HF), cardiomyopathy, Strain characteristics in hypertension and subclinical myocardial damage are investigated less. Not numerous clinical studies have demonstrated predictive value of Strain in respect to CVD complications and outcomes. Very few studies available are available in population, they revealed the association between LV Strain with the risk of acute coronary events, malignant arrhythmias, HF, death from CVD and from all causes (risk coefficients were around 1.3 for CHD, 1.7 for HF and 1.6-2.0 for fatal CVD and total mortality). Conclusion. Strain technology is perspective. Currently, the age- and sex- specific reference values of Strain are still under the question; further studies of LV Strain are warranted for assessment of early systolic dysfunction and investigation of association with CVD risk factors and prognosis.



7.
THE USE OF INTRAVENOUS FORMS OF BETA-BLOCKERS IN ACUTE CORONARY SYNDROME

I.D. Astrakhantseva1, I.A. Urvantseva1, K.Yu. Nikolaev2
1State-Financed Organization Khanty-Mansi Autonomous Region - Ugra District Cardiodispensary «Centre of Diagnosis and Cardiovascular Surgery, 628403, Surgut, Lenin av., 69/1
2Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: acute myocardial infarction, intravenous beta-blockers, metoprolol

Abstract >>
Beta- blockers are actively used in the treatment of patients with chronic and acute ischemic heart disease. Throughout the study period of effects of beta-blockers to limit myocardial necrosis at acute myocardial infarction (AMI) clinical researches were performed under pharmacological reperfusion of the coronary arteries; herewith the data about the clinical efficacy of beta-blockers of the patients with invasive strategy treatment of AMI are limited in international literature. The purpose of this review is to analyze the world literature on the use of injection forms of beta-blockers in acute coronary syndrome. Based on the analysis, it was concluded that the intravenous administration of metoprolol in the acute period of myocardial infarction clearly leads to the restriction of the necrosis zone, reduces the risk of repeated myocardial infarction and reduces the incidence of ventricular fibrillation.