Adipose tissue is an endocrine organ secreting signal peptides adipokines. Adipokines play a significant role in the regulation of the immune, endocrine, nervous, excretory systems. Adipokine imbalance leads to chronic inflammation, metabolic and cardiovascular diseases. Obesity as the primary reason of the adipokine imbalance is the leading risk factor of hypertension, atherosclerosis and coronary artery disease. Thus, experimental and clinical studies of adipokine biology are essential for the development of the novel therapeutic approaches for the management of cardiometabolic diseases. This review focuses on the role of adiponectin, leptin, chemerin, omentin and visfatin in physiological and pathophysiological processes in the cardiovascular system.

Pathogenesis of arterial hypertension (HTN) was predominantly associated with genetics and epigenetics, environment and disturbances in homeostasis systems (autonomous nervous system, immunity, renin-angiotensin system) for a long time. Gut microbiota has recently emerged as a self-controlled factor contributing to or limiting the development of HTN. New data on the role of gut bacteria in the development of HTN, direct blood pressure regulation as well as impact on epigenetics, immunity and renin-angiotensin-aldosterone system of its metabolites are presented.

Objective. To assess the relationship of carriers of risk alleles for the rs9939609 polymorphisms of the FTO gene and rs1225537 of the TCF7L2 gene with the metabolic syndrome (MS) component in a national population sample of three regions (Samara, Orenburg, St Petersburg) as part of the ESSE-RF epidemiological study.

Design and methods. The data of 3 regions were analyzed: Samara, Orenburg and St Petersburg. The total number of patients included in the study was 4 793 people, the average age of the examined was 45,6 ± 11,9 years. All participants in the study underwent an assessment of anthropometric parameters (height, weight, waist circumference), blood pressure and heart rate; serum glucose and lipids were measured, genotyping for the determination of single nucleotide polymorphism (SNP) rs1225537 of the TCF7L2 gene and rs9939609 of the FTO gene polymorphism was performed.

Results. The occurrence and association of genotypes of the FTO and TCF7L2 gene with the components of MS were assessed separately in men and women. In women, the risk allele of the FTO gene was significantly more common among people with abdominal obesity. In males, the risk allele of the FTO gene was associated only with hyperglycemia. In both groups, the risk allele of the TCF7L2 gene was significantly more common in persons with hyperglycemia, while in men, the risk allele of the TCF7L2 gene was also associated with the development of abdominal obesity.

Conclusions. We confirmed the association between the rs9939609 risk allele of the FTO gene with the development of abdominal obesity, as well as the risk allele rs1225537 of the TCF7L2 gene with the development of hyperglycemia in the Russian population. Our study also demonstrated various combinations of components of MS in the group of men and women in carriers of risk alleles s9939609 of the FTO gene and rs1225537 of the TCF7L2 gene.

Objective. The aim of this study was to investigate gender-specific differences in the clinical profile of hypertrophic cardiomyopathy (HCM) and to determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in women and men with HCM.

Design and methods. The study population consisted of 171 patients with HCM ≥ 18 years old. A novel disease pathway model was employed to assess clinical course of HCM. Single nucleotide polymorphism (SNP) rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction assay.

Results. We found no significant gender-specific differences in clinical course of HCM in patients ≥ 18 years old during 10-year follow-up. High prevalence of T allele of rs1739843 of the HSPB7 gene was observed in women > 18 years old with HCM and chronic heart failure (CHF) with preserved ejection fraction (EF) (≥ 50 %) (C: Т, odds ratio (OR) = 0,213, 95 % confidence interval (CI) = 0,077-0,593, p < 0,002). Left atrium (LA) and left ventricle (LV) diastolic diameters were higher and LV diastolic diameter / body surface area was smaller in men than in women with HCM ≥ 18 years old. The frequency of TT genotype of rs1739843 of the HSPB7 gene was greater in men ≥ 18 years old with HCM and CHF III-IV (NYHA) functional class (FC), compared to those with CHF I-II FC (NYHA) (ТТ: ТС + СС, OR = 0,212, 95 % CI = 0,065-0,688, p < 0,03). The allele frequency (С: Т) also differs between HCM male patients with CHF III-IV FC (NYHA), compared to those with CHF I-II FC (NYHA) — 46,9: 53,1 % vs 69,5: 30,5 % (OR = 0,387, 95 % CI = 0,196-0,764, p < 0,006). Men with HCM ≥ 18 years old showed higher T allele frequency in case of HCM progression including those advancing up to CHF III-IV FC (NYHA) and those with CHF III-IV FC (NYHA) + atrial fibrillation.

Conclusions. LA and LV diastolic diameters were smaller and LV diastolic diameter / body surface area was higher in women than in men with HCM ≥ 18 years old. There were no significant gender-specific differences in clinical profile of HCM in patients ≥ 18 years old during 10-year follow-up. Allele T of rs1739843 of the HSPB7 gene is associated with HCM and CHF with preserved ejection fraction (≥ 50 %) in women ≥ 18 years old. The T allele and TT genotype of rs1739843 of the HSPB7 gene is also associated with HCM and CHF III-IV FC (NYHA) in men > 18 years old.

Objective. The aim of the work was to evaluate the expression of the MADD gene during the development of myocardial hypertrophy caused by hemodynamic factors in the model of aortic coarctation, as well as in the model of renovascular arterial hypertension (model “2 kidney — 1 clip”).

Design and methods. The study involved Wistar rats (n = 60) at the age of 8 weeks. Two experimental models of myocardial hypertrophy were used: the aortic coarctation model (n = 30) and the “2 kidneys — 1 clip” model (n = 21). Animals were divided into groups according to the duration of the experiment (1 and 10 weeks), we also formed a group of intact animals (n = 9). Myocardial hypertrophy was verified by echocardiography. After euthanasia and myocardial extraction, the tissues were homogenized in Extract RNA reagent (Evrogen) in order to obtain RNA. A complementary DNA strand was obtained by reverse transcription using Random (dN) 10-primer (Evrogen) and MMLV RT kit (Evrogen) primers. The relative expression level of the MADD gene in rat myocardium was determined using real-time polymerase chain reaction. The expression level was calculated using the ΔΔCt method; the GAPDH and HPRT genes were used as a reference control.

Results. In the aortic coarctation model, MADD gene expression in the 1-week group was significantly higher (p < 0,05) compared with the intact group. In this model, there as a direct correlation of the expression of the MADD gene with NPPA gene, as well as with echocardiography indicators (final systolic size, final diastolic size, and myocardial mass index, p < 0,05), and an inverse relationship between MADD gene expression and the shortening fraction (p < 0,05). The renovascular hypertension model did not show a significant increase in the expression of the MADD gene in myocardium in experimental group compared to intact animals.

Conclusions. The expression of the MADD gene increases mainly under the influence of acute hemodynamic overload, and is likely to be important for the immediate response by cardiomyocytes to pressure load. Correlation was found between the expression level of the MADD gene and such echocardiographic parameters as the shortening fraction, end-diastolic and end-systolic sizes of the left ventricle.

Background. One of the possible methods of reducing pressure in the pulmonary artery (PA) in pulmonary hypertension (PH) is radiofrequency damage of the periarterial nerve fibers. At the same time, the impact of the autonomic nervous system has not been fully determined yet. It is also known that dopamine induces LA vasorelaxation, however, the subtypes of dopamine receptors involved in this mechanism have not yet been identified.

Objective. To assess the morphology of nerve fibers and ganglia in the periarterial adipose tissue of the PA bifurcation in patients with and without PH. Design and methods. Tissue samples of the PA bifurcation zone with surrounding fatty tissue were taken from 8 patients with PH and 9 patients without PH (autopsy material): 7 women aged 59 ± 22 years and 10 men 62 ± 15 years. An immunohistochemical reaction was performed with antibodies to S100 protein, tyrosine hydroxylase (TH), M1 muscarinic receptor, D1, D2, D5 dopamine receptors. The number of nerve fibers and ganglia per area of the preparation, their diameter and depth relative to the PA intima were estimated.

Results. There were no statistically significant differences in the structure and size of nerve fibers and ganglia in patients with and without PH. In general, the average number of nerve fibers per area of the preparation (4 cm2) was 29,1 ± 15,5; ganglia — 1,1 ± 1,3; the average fiber diameter was 130,6 ± 35,1 pm, ganglia — 532,0 ± 790,7 pm; the average fiber-intima distance was 2141,4 ± 663,3 pm, the ganglion-intima — 1799,0 ± 500,5 pm. The density of fibers around the PA bifurcation was significantly higher (p = 0,04) in patients with chronic heart failure (CHF) II NYHA functional class (FC) (20 ± 10 fibers / 4 cm2) compared to patients with CHF III-IV FC (11 ± 4 fibers / 4 cm²). The expression of M1 and TH was determined on nerve fibers and ganglia, in the endothelium and smooth muscle cells of the PA, in the epithelium of the bronchi. At the same time, unlike M1, the expression of TH was not observed in all nerve cells, and its level ranged from 1 to 4 points. No D2 receptor expression was detected, D1 expression was mild, and D5 was 4 points in all cases in the endothelium and smooth muscle cells of the LA.

Conclusions. Morphometric analysis of nerve fibers and ganglia revealed no differences between patients with and without PH. There was a significant decrease in the number of nerve fibers with the progression of heart failure. TH expression on nerve fibers and ganglia was less pronounced and was not observed in all cells as compared with the M1 receptor. Expression of dopamine receptors was detected only in the endothelium and smooth muscle cells of the PA. Further morphological study involving larger sample will allow the substantiation for the validity of the interventional innervation of the PA.

Background. An increase in cardiovascular morbidity and mortality in patients with rheumatological pathology is of great scientific interest in the modern cardiological and rheumatological community.

Objective. The aim of the study was to determine the level of asymmetric dimethylarginine (ADMA) in patients with various rheumatological pathologies, as well as to compare the data with ADMA levels in subjects with asymptomatic atherosclerosis and the group of healthy individuals.

Design and methods. The study involved 3 groups of patients. The first group included patients with various rheumatic diseases (RH): rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, Sjogren’s disease. The second group consisted of patients with cardiovascular risk factors and atherosclerosis (confirmed by the thickening of the intima-media complex more than 0,9 cm and/or the presence of atherosclerotic plaques). These patients had neither history of acute myocardial infarction or acute cerebrovascular accident, nor clinical signs of coronary heart disease. The third group consisted of healthy blood donors.

Results. Our study showed that ADMA level was significantly higher in the RE group than in the control and comparison groups, and was also interrelated with the main traditional cardiovascular risk factors.

Background. In arterial hypertension (HTN), diastolic dysfunction (DD) of the left ventricle (LV) makes a major contribution to the development of heart failure, so the treatment of DD is an important task. The role of the JNK-dependent pathway in myocardial remodeling in HTN is shown.

Objective. To evaluate the effect of the new JNK inhibitor IQ-1S (11H-indeno [1,2-b]quinoxalin-11-one oxime sodium salt) on parameters of cardiac activity in SHR rats during the period of stable HTN and the formation of DD.

Design and methods. The experiments were carried out on 5 normotensive Wistar-Kyoto (WKY) rats and 10 spontaneously hypertensive rats (SHRs); the experiments included animals that reached the age of 12 weeks. IQ- 1S (50 mg/kg) was administered intragastrically daily to the SHRs of the experimental group (n = 5) for 6 weeks. The WKY control animals (n = 5) and the SHRs (n = 5) received an equivolume amount of distilled water. Systolic blood pressure (SBP) was measured before and after the course of IQ-1S. At the end of the IQ-1S course, body mass (BM) and left ventricular mass (LVM) were evaluated, and contractile myocardial activity (intracardiac sensor) was recorded.

Results. Before and after the IQ-1S course, the values of SBP in the control SHRs were higher than in WKY rats by 30 % and 53 %. After the administration of IQ-1S SHRs showed significantly lower SBP (by 13 %), the LVM/BM index (by 5 %) and the end-diastolic LV pressure (by 40 %) compared to the control SHRs.

Conclusions. Our results confirm the ability of the JNK inhibitor IQ-1S to reduce blood pressure, myocardial hypertrophy and suppress the development of diastolic LV dysfunction in SHRs with the stable HTN.

Objective. To identify the effects of youth and aging proteins — GDF11, CCL11, GDF15, JAM-A on cardiohemodynamics in healthy and hypertensive women.

Design and methods. The study involved 102 women. The control group consisted of 30 healthy women. Hypertensives were divided into 2 groups. The first (HTN-1) included 37 women with stage II hypertension (HTN) who received antihypertensive therapy. The second group (HTN-2) included patients who received antihypertensive drugs and regularly underwent kinesitherapy for 2-3 years. The enzyme immunoassay (ELISA) method was performed to determine the levels of GDF11, GDF15, JAM-A and CCL11 proteins. All subjects underwent echocardiography and dynamic light scattering (DLS).

Results. In healthy women, we found a positive correlation between the GDF15 proteins and JAM-A and blood pressure (BP). The GDF11/GDF15 ratio negatively correlated with BP level. In HTN-1 group, a negative relationship was found between the GDF15 level and the mean and pulse systolic pressure. In HTN-2 group, a negative relationship was found between CCL11 protein and pulse pressure, as well as the GDF15/CCL11 ratio and diastolic and positive correlation with the pulse pressure. In healthy subjects, no significant correlations were found between the studied proteins and cardiovascular functions, but GDF11/CCL11 ratio positively correlated with echocardiographic indices: the final systolic and impact volumes. In HTN-2 group, a positive relationship was found between the GDF11/GDF15 ratio and the minute volume, as well as GDF15/CCL11 and systolic shortening. The absolute values of hemodynamic indices (HI) in HTN-1 group were lower than in the control group, indicating a violation of the microcirculation with the trend towards the higher velocities. In HTN-2 group, hemodynamic parameters were close to those in the control group. In healthy individuals, HTN-1 and HTN-2 groups, dozens correlations were found between the studied proteins, their ratios, and various hemodynamic and oscillatory indices.

Conclusions. The levels of the “youth protein” GDF11 and the “aging proteins” GDF15, CCL11, JAM-A, as well as their ratios, exhibit positive and negative relationships with BP and cardiohemodynamic functions. At the same time, the effect of GDF11 and its predominance over CCL11, GDF15 and JAM-A is mostly adaptive.

Objective. To study the association of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) with the development of fatal and non-fatal complications in patients with essential hypertension (EHTN) in the process of mid-term follow-up.

Design and methods. 90 patients with EHTN aged 40 to 75 years (average age 56,4 ± 8,1 years) were observed, including 47 women and 43 men. The follow-up period ranged from 20 to 26 months (median observation — 24 months). At baseline, we assessed height, weight, body mass index, waist circumference, blood pressure and heart rate, fasting glucose, serum creatinine with the estimated glomerular filtration rate by CKD-EPI, lipid profile, serum levels of TNF-α and IL-10 by enzyme-linked immunosorbent tests (“CITOKIN — STIMUL — BEST”, Novosibirsk, Russia).

Results. A cumulative decrease in the proportion of patients with EHTN without development of fatal and non-fatal cardiovascular complications at follow-up was 70,73 %. When analyzing the associations between cytokines and the development of fatal and non-fatal complications in EHTN patients at term follow-up, we found no difference in TNF-α levels in EHTN patients who reached the end-point and patients without complications (8,31 ± 0,97 vs 8,37 ± 1,33 pg/ml, respectively, p > 0,05), while IL-10 level was higher in patients without complications compared to n patients with complicated EHTN (15,9 ± 3,3 vs 13,5 ± 2,3 pg/ml, respectively, p < 0,01). Logistic regression analysis showed that only systolic blood pressure was an independent risk factor associated with the development of EHTN complications during mid-term follow-up: hazard ratio (HR) — 1,03; 95 % confidence interval (CI) 1,00-1,05. In addition, an increase in IL-10 level was an independent anti-risk factor associated with a significant 25 % reduction in the risk of EHTN complications (HR 0,75; 95 % CI 0,57-0,99).

Conclusions. An increased IL-10 concentration was an independent anti-risk factor for the complicated EHTN during mid-term follow-up associated with a 25 % reduction in the risk of fatal and non-fatal complications. At the same time, we did not find the association of the TNF-α level with prognosis in EHTN patients during mid-term follow-up.

The stroke is one of the most serious complications of arterial hypertension (HTN). Genetic markers of the disease can be used to improve the risk stratification. According to the literature data of single nucleotide polymorphism (SNP) rs12204590 (T > A) is a new potential genetic marker for stroke, however, in published studies, cardiovascular pathology preceding stroke was not assessed.

Objective. To study the association of SNP rs12204590 (T > A) with the development of stroke in patients of the East Siberian population with HTN and without HTN. Design and methods. The study involved 260 patients with stroke (age 57,0 [51,0-62,0] years) and 272 patients of the control group (age 55,0 [51,0-62,0] years). Among stroke survivors, there were 157 men and 103 women. The control group included 170 men and 102 women. 249 patients ofthe main group and 177 patients of the control group had HTN. The following risk factors for the development of stroke were present in the main group: paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostasis system. All participants underwent clinical, instrumental and molecular genetic research. Statistical analysis was carried out using the programs Statistica for Windows 7.0, Excel and SPSS 22.

Results. The association of TA genotype SNP rs 122045 90 (T > A) with the development of stroke was confirmed in the main group, as well as in the subgroup of HTN patients who had stroke. An association of the AA genotype with stroke was found in males. Associations of the studied polymorphism with the risk factors for stroke were not identified.

Conclusions. The TA genotype rs12204590 (T > A) reduces the risk of acute stroke compared to the genotypes TT and AA, which is also observed in HTN patients. The AA SNP genotype rs12204590 (T > A) increases the risk of developing stroke in males.

Background. Recent studies have demonstrated possible association between vitamin D deficiency and atherogenic dyslipidemia. However, there are practically no results from Russian investigations in this field.

Objective. To assess serum lipids in women carrying various vitamin D receptor (VDR) gene variants.

Design and methods. The study included 697 women aged between 35 to 55 years (mean age 43,4 ± 0,3 years). Anthropometric data including height, waist circumference, body mass index were measured. Serum lipid profile, 25-hydroxyvitamin D (25(OH)D) level and four VDR gene polymorphisms BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) were evaluated.

The results showed high prevalence of abdominal obesity, dyslipidemia, vitamin D insufficiency/deficiency in the study group and 2,6 increased risk of high-density lipoprotein (HDL) cholesterol reduction in women with vitamin D deficiency. There were no differences in serum 25(OH)D between VDR genotypes. GG (BB) genotype carriers of BsmI (rs1544410) demonstrated higher triglyceride levels than subjects with GA, AA (Bb, bb) genotypes. Women with TT (AA) и TG (Aa) genotypes of ApaI (rs7975232) had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to GG (aa) genotype carriers.

Conclusions. The study revealed the associations between low vitamin D status and decreased HDL cholesterol as well as between BsmI (rs1544410) and ApaI (rs7975232) VDR genotypes and atherogenic dyslipidemia.

Objective. To determine the effect of morbid obesity, impaired carbohydrate metabolism and bariatric surgery on adiponectin and leptin mRNA levels in subcutaneous and visceral adipose tissue.

Design and methods. The study included 30 obese female patients. Eleven patients had co-existent impaired carbohydrate metabolism. The control group consisted of 10 healthy non-obese women. In all obese patients, subcutaneous and visceral adipose tissue samples were taken during bariatric surgery. In obese patients 1 year after the intervention and in control individuals subcutaneous adipose tissue samples were collected. The circulating levels of adiponectin and leptin were determined by the enzyme immunoassay. The amount of adiponectin and leptin mRNA in adipose tissue were analyzed by real-time polymerase chain reaction.

Results. During the first postoperative year, all patients showed a monotonous decrease in body mass index. After the surgery, the circulating levels of adiponectin and leptin returned to reference values (for healthy population). Compared with the control group, obese patients showed 1,4-times lower adiponectin mRNA level (p < 0,01) in subcutaneous adipose tissue, while leptin mRNA level did not change. In obese patients with impaired carbohydrate metabolism, the adiponectin mRNA level was twice lower in visceral adipose tissue (p < 0,01), compared to patients without impaired carbohydrate metabolism. In obese patients with and without impaired carbohydrate metabolism, mRNA levels of adipokines were more than 2-times lower in visceral adipose tissue compared to subcutaneous adipose tissue (p < 0,05). In subcutaneous adipose tissue, 1 year after bariatric intervention, adiponectin mRNA level decreases by 4,5 times (p < 0,01) in obese patients, and leptin mRNA level decreases by 3,1 times (p < 0,01) in patients with obesity and by 1,5 times (p < 0,05) in patients with obesity and impaired carbohydrate metabolism. Neither adiponectin nor leptin mRNA levels from adipose tissue of different localization showed statistically significant correlation. No correlation was found between the levels of circulating adipokines and their mRNA amount in adipose tissue.

Conclusions. Our results indicate that adiponectin and leptin mRNA levels in adipose tissue cells depend on their localization in the body, as well as the presence of obesity and impaired carbohydrate metabolism. We also showed that adiponectin and leptin mRNA levels in adipose tissue change in response to bariatric surgery.