[MicroRNA and obesity. A modern view of the problem (review of literature).] / МикроРНК и ожирение. Современный взгляд на проблему (обзор литературы).

The incidence of obesity is steadily increasing worldwide, reaching the epidemic. Obesity is associated with cardiometabolic diseases through the complex interactions between genetics and epigenetics predisposition, the environment, diet, and lifestyle. However, the molecular mechanisms and factors influencing these processes are not fully known. MicroRNAs are a new class of important regulatory determinants in many biological and pathological processes. There is increasing evidence of the role of miRNAs in the regulation of the functional activity of adipose tissue and the development of obesity. A change in the expression of MicroRNAs can lead to changes in the activity of genes that control a number of biological processes, including inflammation, lipid metabolism, and adipogenesis. Understanding the role of miRNAs in the regulation of adipogenesis and the development of obesity will establish therapeutic targets for the development of new and effective drugs, which will lead to a breakthrough in the fight against obesity and related diseases. This review presents current data on the role of miRNAs in the regulation of the functional activity of adipose tissue, including adipogenesis of white, beige and brown adipocytes, as well as the prerequisites for using miRNAs as biomarkers of obesity and the possibility of therapeutic use.

[Expression of gene and content of adiponectin in fatty tissue in patients with ischemic heart disease]. / Ékspressiia gena i soderzhanie adiponektina v zhirovoi tkani u patsientov s ishemicheskoi bolezn'iu serdtsa.

The purpose of the study was to investigate the features of expression and adiponectin content in the adipocyte culture of subcutaneous, epicardial, and perivascular adipose tissue and the effect of various doses of rosuvastatin on these processes. 29 patients with coronary artery disease were examined. Adipocytes were isolated from the samples of SAT, EAT and PVAT which were taken during coronary artery bypass surgery, followed by cultivation in the presence of rosuvastatin and evaluation of gene expression and adiponectin concentration. Adipocytes SAT, EAT and PVAT differed in the level of adiponectin secretion and expression of its gene. On day 1 of cultivation the expression of the adiponectin gene in the EAT was 2.3 times lower than in the PVAT. On day 2 of cultivation the expression of the adiponectin gene was reduced both in the EAT and the PVAT as compared to the SAT. When rosuvastatin was added at a concentration of 1 mmol/L, adiponectin gene expression in PVAT was higher than when rosuvastatin was added at a concentration of 5 mmol/L, in the adipocyte culture of SAT effect was opposite. Thus, the adipocytes of EZhT and, to a greater extent, PAS, can be a therapeutic target for statins in the case of the pathological activation of adipose tissue.

The marker of adverse prognosis 1.5-anhydroglucitol in patients with coronary heart disease in the long-term period after planned myocardial revascularization.

AIM: Determination of the prognostic value of 1.5-anhydroglucitol (1.5-AG) for the development of cardiovascular events in patients with coronary heart disease (CHD) within a year after a planned percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A prospective study was conducted in Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovascular Disease among 149 patients admitted to planned PCI in the period from 2016 to 2017. Criteria for inclusion in the study: age up to 70 years, angina I-IV functional classes or post-infarction cardiosclerosis, the presence of indications for planned PCI. -Exclusion criteria from the study: previous myocardial revascularization; prosthetic heart valves; decompensation of chronic heart failure, anemia of any degree; acute coronary syndrome in index hospitalization; exacerbation of somatic diseases. The results of the research were processed by Statistica Windows 6.0. RESULTS: During the year after planned PCI, 39 (26.14%) cardiovascular events were registered in patients with CHD, of whom more than half of the cases (51.28%) were associated with the presence of indications for PCI of de novo. Lower levels of 1.5-AG were observed in the group of patients with cardiovascular events (p=0.000). When patients were divided according to median of the studied marker patients with a concentration of 1.5-AG less 20.96 µg/ml (before PCI) were more likely to have PCI after restenosis of the stent, compared with patients whose median concentration of this marker was higher (p=0.028). The logistic regression method revealed a significant direct relationship reflecting the prognostic value of lower concentration of 1.5-AG in relation to the development of cardiovascular events in patients regardless of the presence of carbohydrate metabolism disorders [OR 0.25 (0.10-0.62)]. CONCLUSION: According to the results of the study, the prognostic value of the concentration of 1.5-AG less 20.96 µg/ml was established in relation to the development of cardiovascular events in patients with CHD during the year after a planned PCI, regardless of the presence of carbohydrate metabolism disorders.

The role of perivascular adipose tissue in the development of cardiovascular diseases. The importance of diagnosis for assessing the risk stratification of cardiovascular diseases.

Obesity is closely associated with metabolic and cardiovascular diseases, including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue (AT) is identified as a complex endocrine organ, with a wide range of regulatory functions at the cellular, tissue and systemic levels. Various terms, including paracardiac, epicardial and pericardial, are used to describe the fatty deposits surrounding the heart. Among all the fat depots, perivascular AT (PVAT) is of great biological significance for the cardiovascular system due to its anatomical proximity to the vessels. Recent studies have shown the presence of a complex, bidirectional paracrine and vasocardial signaling system between the vascular wall and PVAT. In the review, we will discuss the biological role of PVAT in both the physiological state and cardiovascular pathology, emphasizing its dual proatherogenic and antiatherogenic role. Let us consider PVAT as a target for various therapeutic agents in cardiovascular diseases. We will also analyze data on the role of non-invasive techniques as a diagnostic tool for assessing coronary artery inflammation.

Adipokine and Cytokine Profiles of Epicardial and Subcutaneous Adipose Tissue in Patients with Coronary Heart Disease.

The content of adipokines, pro- and anti-inflammatory cytokines were studied in adipocytes isolated from epicardial and subcutaneous adipose tissue of 24 coronary heart disease patients. The content of leptin and soluble leptin receptor in adipocytes of epicardial adipose tissue was higher by 28.6 and 56.9% and the level of adiponectin was lower by 33% than in adipocytes of the subcutaneous fat. In culture of epicardial adipocytes, the levels of proinflammatory cytokines TNF-α and IL-1 were higher. Subcutaneous adipose tissue adipocytes were characterized by higher levels of anti-inflammatory cytokines IL-10 and FGF-ß. In epicardial adipocytes of coronary heart disease patients, the concentrations of leptin, TNF-α, and IL-1 were higher, while the levels of defense regulatory molecules (adiponectin, IL-10, and FGF-ß) were lower than in subcutaneous adipocytes.

[The advantage of test on thrombin generation for evaluation of hemostasis potential under implementation of coronary bypass surgery in patients with ischemic heart disease.]

The purpose of study is to evaluate peri-operational parameters of testing of generation of thrombin and its relationship with indices of coagulation hemostasis, fibrinolytic system and anti-coagulants in patients with ischemic heart disease under coronary bypass surgery in conditions of artificial blood circulation. The examined sampling included 200 patients with ischemic heart disease. The planned primary operation of coronary bypass surgery in conditions of artificial blood circulation was applied to all of them. The testing of generation of thrombin was implemented using automated analyzer CEVERON-ALPHA (Technoclone, Vienna, Austria). The indices of testing of generation of thrombin were compared with common techniques of evaluation of hemostasis (INR, PTT, fibrinogen, Qick's prothrombin testing, thrombin time, AT-III, protein C, factor VIII), von Willebrand factor, inhibitor of activation of plasminogen type I (PAI-I), tissue and urokinase plasminogen activator. It is demonstrated that application of testing of thrombin generation duplicates enumerated indices and permits at the same time instant to detect both pro-coagulation and anti-thrombotic shifts. The advantage of testing of thrombin generation is in evaluation of thrombin potential that is most actual in cardiologic practice.

[The physiologic and pathophysiologic role of stimulating growth factor ST2.]

The ST2 is a member of family of receptors of interleukin I (IL-I) and consists of two isoforms: a trans-membrane of cellular one (ST2L) and soluble or circulating one (sST2). The ST2 is a receptor of IL-33 that represents IL-I like cytokine. The IL-33 manifests its cellular functions binding receptor complex consisted of accessory protein ST2L and IL-IR. The system IL-33/ST2 is activated in cardiomyocytes and fibroblasts in response to mechanical irritation or damage. It was demonstrated that interaction between IL-33 and ST2L is a cardioprotective one. The experimental models were used to demonstrate decreasing of myocardium fibrosis, prevention of development of hypertrophy of cardiomyocytes, decreasing of apoptosis and amelioration of functional capacity of myocardium at interaction of IL-33 and ST2L. In particular, the positive effects of IL-33 are related to receptor of ST2L. In turn, sST2 by binding with IL-33 sets blocking of interaction between IL-33/ST2L hence eliminating cardioprotective effects. During last years, the knowledge about the role of ST2 in pathophysiology of cardio-vascular diseases broadened and now the role of ST2 is related to myocardium dysfunction, fibrosis and remodeling. The system IL-33/ST2L, besides its myocardial role, can play an additional role in development and progressing of atherosclerosis. The system IL-33/ST2L can have a therapeutic potential in case of myocardial overload or trauma. On the contrary, sST2 acts as a false receptor of IL-33 blocking cardioprotective effects of interaction of IL-33/ST2L.

[Diagnostic value of the stimulating growth factor ST2 during hospitalization for myocardial infarction]. / Diagnosticheskoe znachenie stimuliruyushchego faktora rosta ST2 v gospital'nom periode infarkta miokarda.

AIM: To determine the concentration of the stimulating growth factor ST2 and its relationship to the clinical course of myocardial infarction (MI) over time during hospitalization. MATERIALS AND METHODS: Eighty-eight MI patients whose mean age was 59±8.36 years were examined. On days 1 and 12 of MI, the serum levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were determined by ELISA. A control group consisted of 30 people. RESULTS: On day 1 of hospitalization for MI, the concentrations of ST2 and NT-proBNP were higher 2.4 and 4.5 times, respectively, than those in the controls; by day 12, there was a statistically significant decrease in the level of ST2 while that of NT-proBNP was unchanged. During hospitalization, the investigators recorded MI complications, according to which the patients were divided into favorable and unfavorable MI groups. On day 1 of hospitalization, the level of ST2 in the patients with unfavorable MI was twice higher than in those with favorable MI and 3.7 times higher than in the control group. On day 12, both favorable and unfavorable MI groups showed a reduction in the level of the marker. On day 1 of MI, the concentration of NT-proBNP in the patients with a poor prognosis was 6.8 times greater than in the controls and 1.8 times more than in the patients with a good prognosis. On day 12, NT-proBNP levels remained elevated in both groups. Logistic regression analysis revealed that the determination of ST2 in combination with NT-proBNP increased their diagnostic significance (odds ratio, 1.92; 95% CI, 1.7-3.2; area under characteristic curve, 0.89; p=0.004). CONCLUSION: The level of ST2 was a more sensitive indicator of hospitalization for MI than that of NT-proBNP. The combined use of ST2 and NT-proBNP was found to have a high diagnostic sensitivity and specificity.

[Evaluation of the hemostatic potential at coronary artery bypass surgery during long-term aspirin therapy]. / Otsenka gemostaticheskogo potentsiala krovi pri operatsiyakh koronarnogo shuntirovaniya na fone dlitel'noi terapii atsetilsalitsilovoi kislotoi.

AIM: To estimate thrombin generation test parameters in patients with coronary heart disease during coronary artery bypass surgery under extracorporeal circulation after transfusion of donor platelet concentrates during long-term therapy with acetylsalicylic acid (ASA). SUBJECTS AND METHODS: A total of 148 patients with coronary heart disease who had undergone elective primary coronary artery bypass surgery under extracorporeal circulation during preserved therapy with ASA (75-100 mg/day) were examined. According to donor platelet concentrate transfusion, all the patients were divided into 2 groups: 1) 76 patients undergoing donor platelet transfusion and 2) 72 without this procedure. A control group consisted of 20 apparently healthy individuals. At the pre-, intra-, and early postoperative stages, the investigators evaluated the following thrombin generation test parameters: lag time (min); peak thrombin concentration (nM/l); time to peak (min); the area under the thrombin generation curve (nM), and thrombin generation rate (nM/min). RESULTS: During long-term ASA therapy, the patients were found to have an activated endogenous thrombin potential in the pre- and intraoperative periods, as evidenced by the high peak concentration of thrombin and the increased rate of its generation. At the same time, the time of prothrombinase complex activation and that of thrombin generation were longer than those in the control group. In the early postoperative period, the patients who had not been transfused with platelet concentrates with a further increase in the temporal parameters, showed a decreased hemostatic potential, reaching the control level, whereas donor platelet transfusion stimulated endogenous thrombin generation: the time to initiate clotting and that to reach the peak were shorter; in this case, the thrombin generation rate and concentrations increased, but the preoperative level was not reached. No perioperative (hemorrhagic or thrombotic ischemic) events were noted in the examined groups. CONCLUSION: The hemostatic potential was preserved in patients receiving long-term therapy for ASA. Taking into account laboratory and clinical findings, platelet concentrate transfusions are unnecessary for preventive purposes. The appropriateness of donor platelet transfusion should be strictly individually approached with regard to the laboratory parameters of the thrombin generation test, by minimizing the risk of perioperative ischemic and hemorrhagic events in each specific patient.

[The possibility of application of stimulant growth factor (ST2) for verifying postinfarction remodeling of myocardium.]

PURPOSE OF STUDY: To detect level ST2 in blood serum of patients with myocardium infarction in dynamics of hospital period and their relationship with remodeling of myocardium. MATERIALS AND METHODS: The study sampling included 87 patients (65 males and 22 females) with myocardium infarction and the ST-segment elevation and average age of 59 years. All patients were allocated in two groups: with adaptive alternative of remodeling of myocardium (67 patients) and deadaptive alternative (20 patients). The control group consisted of 30 individuals. At the first and twelfth days after myocardium infarction in blood serum content of ST2 and NT-proBNP were detected using immune-enzyme technique with application of test-systems produced by Critical Diagnostics (USA) and Biomedica (Slovakia) correspondingly. The data statistical analysis was processed using non-parametric criteria. THE RESULTS: He content of ST2 and NT-proBNP at the first day of myocardium infarction increased in 2.4 and 4.5 times correspondingly as compared with control group. The patients with deadaptive remodeling were characterized by in 1.5 times higher content of ST2 at the first day than in group of adaptive remodeling and in 5.3 times higher that in control group. In the end of hospital period (twelfth day) in both groups decreasing of level of ST2 was observed. The concentration of NT-proBNP at the first day was increased in 1.8 times in patients of both groups and decreased at twelfth day. At that there were no differences between both groups. The high level of ST2 at the first day increases the risk of development of deadaptive remodeling in 4.5 times, NT-proBNP only in 2.3 times. CONCLUSION: The high level of stimulant growth factor ST2 at the first day of myocardium infarction was associated with deadaptive alternative of post-infarction remodeling that permits using ST2 as prognostic marker with high sensitivity and specificity.

[THE SYSTEM OF SOLUBLE LEPTIN RECEPTORS AND PROINFLAMMATORY FACTORS IN MYOCARDIAL INFARCTION].

The present study was motivated by the lack of data on the role ofvariations in the levels of leptin and its soluble receptors and their interaction with proinflammatory factors in the development of acute coronary syndrome. The study included patients suffering myocardial infarction with and without type 2 diabetes mellitus. Hyperleptinemia and its relationship with myocardial necrosis markers (creatine phosphokinase, creatine phosphokinase-MB, troponin) give reason to suggest the important role of leptin in the development of inflammatory process associated with myocardial infarction in patients with and without diabetes mellitus. The results of the study provide a basis for the elaboration of a new therapeutic strategy for the correction of metabolic disorders in patients with acute coronary syndrome.

[The markers of lipid transport system of blood and annual prognosis of cardiac infarction].

The sampling included 133 patients with diagnosis of cardiac infarction with peak of segment ST. After a year after old cardiac infarction, in 38 patients were established such unfavorable outcomes of disease as progressive stenocardia, decompensation of cardiac failure, repeated cardiac infarction and lethal outcome. It is established that among all indicators of lipid profile detected at hospital period of cardiac infarction only three indicators are prognostically significant in groups of patients with different outcomes--levels of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them. During hospital period, augmentation of concentration of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them increases risk of development of distant complications of cardiac infarction. The mathematical model is proposed comprising as predictors free fatty acids and antibodies to oxidized modified lipoproteins of low density. This model makes it possible on the basis of biochemical data obtained during hospital period, to calculate individual cumulative risk and to develop long-term prognosis of probable outcome of cardiac infarction.