The burden of heart failure (HF), developing after myocardial infarction MI, still represents a major issue in clinical practice. Failure of appropriate resolution of inflammation during post-myocardial injury is associated with unsuccessful left ventricular remodeling and underlies HF pathogenesis. Cells of the immune system have been shown to mediate both protective and damaging effects in heart remodeling. This ambiguity of the role of the immune system and inconsistent results of the recent clinical trials question the benefits of anti-inflammatory therapies during acute MI. The present review will summarize knowledge of the roles that different cells of the immune system play in the process of post-infarct cardiac healing. Data on the phenotype, active molecules and functions of the immune cells, based on the results of both experimental and clinical studies, will be provided. For some cellular subsets, such as macrophages, neutrophils, dendritic cells and lymphocytes, an anti-inflammatory activity has been attributed to the specific subpopulations. Activity of other cells, such as eosinophils, mast cells, natural killer (NK) cells and NKT cells has been shown to be highly dependent of the signals created by micro-environment. Also, new approaches for classification of cellular phenotypes based on the single-cell RNA sequencing allow better understanding of the phenotype of the cells involved in resolution of inflammation. Possible perspectives of immune-mediated therapy for AMI patients are discussed in the conclusion. We also outline unresolved questions that need to be solved in order to implement the current knowledge on the role of the immune cells in post-MI tissue repair into practice.

Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation. This review discusses the role of nitric oxide (NO) in the regulation of platelet adhesion and aggregation processes. NO is synthesized both in endotheliocytes, smooth muscle cells, macrophages, and platelets. Modification of platelet NO-synthase (NOS) activity in MetS patients can play a central role in the manifestation of platelet hyperactivation. Metabolic changes, accompanying T2DM, can lead to an abnormal NOS expression and activity in platelets. Hyperhomocysteinemia, often accompanying T2DM, is a risk factor for cardiovascular accidents. Homocysteine can reduce NO production by platelets. This review provides data on the insulin effects in platelets. Decrease in a number and sensitivity of the insulin receptors on platelets in T2DM can cause platelet hyperactivation. Various intracellular mechanisms of anti-aggregating insulin effects are discussed. Anti-aggregating effects of insulin are mediated by a NO-induced elevation of cGMP and upregulation of cAMP- and cGMP-dependent pathways. The review presents data suggesting an ability of platelets to synthesize humoral factors stimulating thrombogenesis and inflammation. Proinflammatory cytokines are considered as markers of T2DM and cardiovascular complications and are involved in the development of dyslipidemia and insulin resistance. The article provides an evaluation of NO-mediated signaling pathway in the effects of cytokines on platelet aggregation. The effects of the proinflammatory cytokines on functional activity of platelets are demonstrated.

Changes in the structural and functional characteristics of the epicardial adipose tissue (EAT) are recognized as one of the factors in the development of cardiometabolic diseases. However, the generally accepted quantitative assessment of the accumulation of EAT does not reflect the size of adipocyte and presence of adipocyte hypertrophy in this fat depot. Overall contribution of adipocyte hypertrophy to the development and progression of coronary atherosclerosis remains unexplored. Objective: To compare the morphological characteristics of EAT adipocyte and its sensitivity to insulin with the CAD severity, as well as to identify potential factors involved in the realization of this relationship. The present study involved 24 patients (m/f 16/8) aged 53–72 years with stable CAD, who underwent coronary artery bypass graft surgery. Adipocytes were isolated enzymatically from EAT explants obtained during the operation. The severity of CAD was assessed by calculating the Gensini score according to selective coronary angiography. Insulin resistance of EAT adipocytes was evaluated by reactivity to insulin. In patients with an average size of EAT adipocytes equal to or exceeding the median (87 μm) the percentage of hypertrophic adipocytes was twice as high as in patients in whom the average size of adipocytes was less than 87 μm. This group of patients was also characterized by the higher rate of the Gensini score, lower adiponectin levels, and more severe violation of carbohydrate metabolism. We have revealed direct nonparametric correlation between the size of EAT adipocytes and the Gensini score (rs = 0.56, p = 0.00047). The number of hypertrophic EAT adipocytes showed a direct nonparametric correlation with the Gensini score (rs = 0.6, p = 0.002). Inverse nonparametric correlations were found between the serum adiponectin level and size (rs = −0.60, p = 0.001), hypertrophy of adipocytes (rs = −0.67, p = 0.00), and Gensini score (rs = −0.81, p = 0.00007). An inverse nonparametric correlation was found between the Gensini score and sensitivity of EAT adipocytes to insulin, estimated by the intracellular redox response (rs = −0.90, p = 0.037) and decrease in lipolysis rate upon insulin addition (rs = −0.40, p = 0.05). The intracellular redox response of adipocytes to insulin was directly correlated with fasting insulin and inversely with postprandial insulin. Our data indicate that the size and degree of hypertrophy of the epicardial adipocytes are related to the CAD severity. According to our results, insulin resistance of adipocytes may be considered as one of the factors mediating this relationship.

The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

ВведениеП о данным Всемирной организации здравоохра-нения (ВОЗ), с 1980 г. число лиц во всем мире, страдающих ожирением, более чем удвоилось. В 2014 г. более 1,9 млрд людей в возрасте 18 лет и старше имели избыточный вес, из этого числа свыше 600 млн страдали от ожирения [1]. Эпидемия ожирения стала одной из наиболее важных проблем, лежащих в основе развития сердечно-сосудистых заболеваний (ССЗ) и метаболических нарушений, таких как артериальная гипертензия, инсулинорезистентность, дислипидемия. Данные об ассоциации ожирения с кардиоваскуляр-ными заболеваниями до настоящего времени неодно-значны и противоречивы. Многие популяционные исследования демонстрируют парадоксальные выводы относительно прогностического значения ожирения ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», Томск Кологривова И.В.*, Винницкая И.В., Кошельская О.А., Суслова Т.Е.Вопрос прогностического значения ожирения в развитии сердечно-сосудистых заболеваний до сих пор остается открытым. Различный вклад висцеральной и подкожной жировой ткани в формирование кардиометаболического риска освещен во мно-гих исследовательских работах. Данные ряда эпидемиологических исследований подтверждают связь висцерального ожи-рения с формированием аномального метаболического профиля и повышенным сердечно-сосудистым риском, в то время как подкожной жировой ткани приписывают относительные протективные свойства. Патофизиологические механизмы, опосредующие связь висцерального ожирения с развитием атеросклероза, остаются недостаточно изученными. Установлено, что половые гормоны, эстрогены и андрогены принимают участие в перераспределении жировой ткани, поддержании энер-гетического гомеостаза, оказывают влияние на секрецию адипокинов и иммунорегуляцию жировой ткани. При этом широко представленные в жировой ткани клетки иммунной системы, в том числе и адаптивного иммунитета, вносят вклад в развитие системного воспаления при ожирении и участвуют в атерогенезе. По данным последних исследований, нарушение продукции стероидных гормонов может быть взаимосвязано с развитием локального субклинического воспаления и влиять на характер кардиометаболических эффектов жировой ткани. В обзоре обсуждаются возможные механизмы, за счет которых осущест-вляется данная взаимосвязь и реализуется сердечно-сосудистый риск при ожирении. The issue of the prognostic value of obesity in the development of cardiovascular diseases still remains open. Different input of visceral and subcutaneous adipose tissue in the formation of cardiometabolic risk is highlighted in many research works. A range of epidemiological studies provides data confirming relation of the visceral adiposity with abnormal metabolic profile and increased cardiovascular risk, while subcutaneous adipose tissue is attributed with relative protective properties. Pathophysiological mechanisms mediating interconnection of visceral adiposity with the development of atherosclerosis remain studied incompletely. It was stated that sex hormones, estrogens and androgens, participate in the redi...

Background: Monocytes are recognized as central cells in the progression of atherosclerosis, and are subcategorized into classical (CD14++CD16 lo), intermediate (CD14++CD16 hi) and non-classical (CD14+CD16 hi) subsets. Purpose: The present study aimed to assess the relationships between different subsets of monocytes, metabolic and inflammatory factors in patients with stable coronary heart disease. Methods: A total of 26 patients (both men and women) with stable ischemic heart disease (IHD) were recruited. Among all the recruited patients, 17 patients had significant coronary artery disease defined as diameter stenosis more than 70%. Severity of CHD was assessed by the Gensini score (GS). Counts of CD14++CD16 lo , CD14++CD16 hi , and CD14+CD16 hi monocytes were evaluated by flow cytometry. Gating was verified and expression of CD163 was determined by imaging flow cytometry. Key cardiac markers, cytokines, and chemokines were detected in serum and in 24-hour-culture medium for peripheral blood mononuclear cells (PBMC) by multiplex analysis. The Mann-Whitney U-test and Spearman's rank correlation coefficient (r) were used for statistical analysis. Results: Patients with stenosis <70% tended to have higher frequency of CD14+CD16 hi monocytes compared to patients with coronary artery stenosis >70%. The frequencies of CD163+CD14++CD16 hi and CD163+CD14+CD16 hi monocytes were elevated in patients with stenosis >70%. In patients with stenosis <70%, the frequency of classical monocytes positively correlated and the frequency of non-classical monocytes negatively correlated with the value of GS (R ¼ 0.757; p ¼ 0.018 and R ¼-0.757; p ¼ 0.018, respectively). Conclusions: In patients with ischemic heart disease, the frequency of classical monocytes was directly correlated with the severity of atherosclerosis, while the frequency of non-classical monocytes was correlated inversely. The effects of these monocyte subsets in the development of myocardial ischemia still need to be elucidated.

Purpose. This work investigates the relations between the production of reactive oxygen species (ROS) by epicardial adipose tissue (EAT) adipocytes and parameters of glucose/insulin metabolism, circulating adipokines levels, and severity of coronary atherosclerosis in patients with coronary artery disease (CAD); establishing significant determinants describing changes in ROS EAT in this category of patients. Material and methods. This study included 19 patients (14 men and 5 women, 53–72 y.o., 6 patients with diabetes mellitus type 2; 5 patients with prediabetes), with CAD, who underwent coronary artery bypass graft surgery. EAT adipocytes were isolated by the enzymatic method from intraoperative explants obtained during coronary artery bypass grafting. The size of EAT adipocytes and ROS level were determined. Results. The production of ROS by EAT adipocytes demonstrated a direct correlation with the level of postprandial glycemia (rs = 0.62, p < 0.05), and an inverse correlation with serum adiponectin (rs = −0.50, p = 0.026), but not with general and abdominal obesity, EAT thickness, and dyslipidemia. Regression analysis demonstrated that the increase in ROS of EAT adipocytes occurs due to the interaction of the following factors: postprandial glycemia (β = 0.95), postprandial insulin (β = 0.24), and reduced serum adiponectin (β = −0.20). EAT adipocytes in patients with diabetes and prediabetes manifested higher ROS production than in patients with normoglycemia. Although there was no correlation between the production of ROS by EAT adipocytes and Gensini score in the total group of patients, higher rates of oxidative stress were observed in EAT adipocytes from patients with a Gensini score greater than median Gensini score values (≥70.55 points, Gr.B), compared to patients with less severe coronary atherosclerosis (<70.55 points, Gr.A). Of note, the frequency of patients with diabetes and prediabetes was higher among the patients with the most severe coronary atherosclerosis (Gr.B) than in the Gr.A. Conclusion. Our data have demonstrated for the first time that systemic impairments of glucose/insulin metabolism and a decrease in serum adiponectin are significant independent determinants of oxidative stress intensity in EAT adipocytes in patients with severe coronary atherosclerosis. The possible input of the interplay between oxidative stress in EAT adipocytes and metabolic disturbances to the severity of coronary atherosclerosis requires further investigation.

Background: The study of laboratory biomarkers that reflect the development of adverse cardiovascular events in the postinfarction period is of current relevance. The aim of the present study was evaluation of oncostatin M (OSM) concentration changes in the early and late stages of myocardial infarction and evaluation of the possibility of its use in prediction of adverse left ventricular remodeling in patients with myocardial infarction with ST-elevated segment (STEMI). Methods: The study involved 31 patients with STEMI admitted in the first 24 hours after the onset of MI and 30 patients with chronic coronary artery disease as a control group. Echocardiographic study was performed on day 3 and in 6 months after STEMI. The serum levels of biomarkers were evaluated on the day of hospital admission and 6 months after MI using multiplex immunoassay. Results: OSM level increased during the first 24 h after the onset of the disease, with the following decrease in 6 months. OSM concentration at admission had correlated with echocardiography parameters and Nt-porBNP, troponin I, CK-MB levels. Our study has demonstrated association of the increased levels of OSM at the early stages of STEMI with development of the adverse LV remodeling in 6 months after the event. Conclusion: Elevation of OSM levels in the first 24 h after STEMI is associated with the development of the adverse LV remodeling in the long-term post-infarction period.