The aim – to identify associations of serum adipokines and metabolic hormones with metabolic indices in abdominal obesity. Material and methods. 151 people aged 25–65 years were included in the study. Questionnaires, anthropometry, blood pressure measurements, and fasting venous blood sampling were performed. The parameters of the lipid profile and glucose in the blood were determined using enzymatic methods. Multiplex analysis was used to determine the level of the following adipokines and metabolic hormones in the blood: adiponectin, adipsin, lipocalin-2, plasminogen activator type 1 inhibitor (PAI-1), resistin, amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, insulin, pancreatic polypeptide (PP), peptide YY (PYY), interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), secretin. Results. An inverse relationship was found between elevated TyG, LAP, and TG/HDL-C indices and serum adiponectin levels, elevated LAP and VAI indices directly depended on serum leptin levels, and an increase in the LAP index ≥ 32 was directly associated with the concentration of serum PAI-1 and C-peptide.
The aim of the study was to examine the relationships between adipokine levels and elevated low-density lipoprotein cholesterol (LDL-C) in individuals aged 25–44 years, with and without abdominal obesity (AO). Material and methods . The study included individuals aged 25–44 years, divided into groups based on the presence/absence of AO and LDL-C levels. Anthropometric parameters, lipid profile (LDL-C, HDL-C, TG, total cholesterol), carbohydrate metabolism markers, and concentrations of certain adipokines were assessed. Statistical data processing was performed using the SPSS 13.0 software package. Results . In all groups of individuals with LDL-C ≥ 3.0 mmol/L, atherogenic changes in the lipid profile, increased blood pressure and glucose levels were observed; however, the severity of concomitant metabolic disorders depended on the presence of AO. Levels of plasminogen activator inhibitor type 1 (PAI-1) (OR 1.010, 95 %, CI 1.000–1.019, p = 0.047) and C-peptide (OR 1.262, 95 %, CI 1.053–1.512, p = 0.012) demonstrated statistically significant associations with elevated LDL-C, regardless of WC. However, when including both molecules in the model, associations were obtained only for C-peptide (OR 1.416, 95 %, CI 1.079–1.858, p = 0.012) and age (OR 1.038, 95 %, CI 1.011–1.065, p = 0.006). Conclusions . Young individuals with LDL-C ≥ 3.0 mmol/L are more likely to exhibit signs of metabolic dysfunction and abnormal visceral adipose tissue activity, manifested by elevated adipocytokines. In young individuals, the risk of having hyperLDL-C is associated with increasing age and elevated C-peptide and PAI-1 levels, regardless of gender or the presence of AO.
Proteomic studies have made a significant contribution to the study of the pathogenesis of cardiovascular diseases, creating the basis for the development of new potential biomarkers for assessing the risk of developing diseases and their complications. We analyzed the main foreign and domestic publications over the past 15 years using the PubMed/Medline and RSCI/elibrary.ru databases and summarized the available data on proteomic studies in the field of atherosclerotic cardiovascular diseases and coronary atherosclerosis. In this literature review, priority was given to studies on the search for new proteomic biomarkers of coronary atherosclerosis, including proteomic markers of unstable atherosclerotic plaques. The data from our own proteomic studies on potential biomarkers of coronary atherosclerosis are presented.
Aim. To determine the associations of serum adipokines (leptin, adiponectin, leptin/adiponectin index (L/A)) and trait anxiety (TA) in individuals aged 25-44.Material and methods. This cross-sectional survey of a random representative sample of individuals aged 25-44 in the Oktyabrsky District of Novosibirsk was conducted at the Research Institute of Internal and Preventive Medicine, a branch of the Institute of Cytology and Genetics, during 2013-2016. A total of 933 persons (43,7% men) were examined (response rate 71% of 1314 respondents). General examination and medical history collection were conducted using standard methods included in the WHO MONICA-psychosocial program. TA was assessed using the State-Trait Anxiety Inventory. Biochemical research was performed in the Laboratory of Clinical Biochemical and Hormonal Studies of Internal Diseases.Results. Among individuals with a high level of anxiety, there are the highest median levels of serum leptin (6573,7 pg/ml) than with a moderate (5017,7 pg/ml) and low(4171 pg/ml) levels of anxiety. The median L/A index is higher with a high level of TA of 167,7 than with a moderate (74,5) and low (72,2) TA (p=0,002). Median serum adiponectin levels were lower among individuals with high anxiety (33,2 μg/ml) compared to those with moderate (38,9 μg/ml) and low (40,8 μg/ml) anxiety levels. A positive correlation was found between TA and leptin and L/A index, as well as a negative correlation between TA and adiponectin.Conclusion. Associations were found between high TA and elevated leptin levels, the leptin/adiponectin ratio, and lower adiponectin levels in individuals aged 2544 years.
Aim. To study the effect of extended-release (XR) metformin after 12 months of use on humoral cardiometabolic markers, parameters of lipid peroxidation (LPO) and vascular stiffness in patients with chronic heart failure with preserved ejection fraction (CHpEF), prediabetes and abdominal obesity (AO). Design. A single-center, open-label, randomized, controlled clinical trial. Materials and methods. The PredMet study included 64 patients (50% men) with CHpEF, prediabetes, and AO. The patients were divided into two groups: group A — metformin XR at a dose of 1000–1500 mg per day for 12 months on the background of standard CHpEF therapy; group B — standard CHpEF therapy. Humoral cardiometabolic parameters (levels of the soluble form of interleukin 33 receptor (soluble ST2), N-terminal propeptide of natriuretic hormone (NT-proBNP), highly sensitive C-reactive protein, hs CRP), oxidative stress parameters (baseline level of malondialdehyde (MDA) in low-density lipoproteins (LDL) and their resistance to oxidation) and the radial augmentation index. Results. After 12 months of the main follow-up period in group A, the level of NT-proBNP decreased by 1.5% (p = 0.007), and the serum hs CRP decreased by 20.7% (p = 0.021) from the baseline values. The concentration of MDA, estimated directly in LDL, when taking metformin XR against the background of standard CHpEF therapy decreased by 4% (p = 0.018), and the content of MDA in LDL after incubation with copper ions decreased by 0.3% (p = 0.035). In group B, on the contrary, there was an increase in the basal level of MDA in LDL by 0.7% (p = 0.044) and its value after incubation of LDL with copper ions by 6.1% (p = 0.009). The levels of soluble ST2 and the radial augmentation index did not differ at visits 1 and 3 in both groups. Conclusion. Taking metformin XR for 12 months at a dose of 1000–1500 mg per day in addition to standard CHpEF therapy in patients with prediabetes and AO is associated with a decrease in markers of inflammation and LPO, as well as a decrease in the level of NT-proBNP. Keywords: extended-release metformin, chronic heart failure with preserved ejection fraction, N-terminal propeptide of natriuretic hormone, malondialdehyde, radial augmentation index
The aim of study was to study the features of the adipokine blood profile in young people with comorbid pathology.Material and methods. A cross-sectional population survey of Novosibirsk was conducted. The population sample included 1415 people, including 47 % of men. Comorbid pathology was considered a combination of 3 or more pathological conditions (CHD, AG, CB, hyperLDL-C, decreased renal function and type 2 diabetes). Adipokine levels in the blood were determined using the multiplex analysis method on a Milliplex multiplex analyzer (Merck, Millipore).Results. When conducting a univariate logistic regression analysis, it was found that the presence of comorbid pathology was associated with an increase in amylin by 1 pg/ml (p < 0.0001), ghrelin by 1 pg/ml (p = 0.016), resistin by 1 ng/ml (p = 0.001), IL-6 by 1 pg/ml (p = 0.005), C-peptide by 1 ng/ml (p = 0.024) and a decrease in PYY by 1 pg/ml (p = 0.007). In multivariate regression analysis in model 1 (gender, age, OT, resistin, IL-6, and PYY), the chance of having comorbid pathology increased by 15 % with an increase in age by 1 year (p = 0.011) and by 2.5 % with a decrease in PYY by 1 pg/ml (p = 0.005); in model 2 (gender, age, WC, resistin, IL-6, and C-peptide), the chance of having a comorbid pathology increased by 13 % with an increase in age by 1 year (p = 0.001), by 0.1 % with an increase in resistin levels by 1 ng/ml (p = 0.046), by 12 % with an increase in IL-6 levels by 1 pg/ml (p = 0.041), and by 116 % with an increase in C-peptide levels by 1 ng/ml (p = 0.019).Conclusions. In young people, the presence of comorbid pathology is associated with an increase in the blood of amylin, ghrelin and a decrease in the level of PYY, responsible for appetite regulation, as well as with an increase in the levels of resistin, IL-6 and C-peptide, involved in the formation of insulin resistance.
The aim. To identify associations between proinflammatory cytokines of visceral adipose tissue with metabolic disorders in abdominal obesity.Materials and methods. The study was conducted on 101 people aged 25–65 years. Questionnaires, anthropometry, blood pressure measurements, as well as fasting blood sampling and visceral adipose tissue biopsies during elective surgery were conducted. Enzymatic methods were used to determine the parameters of the lipid profile and glucose in the blood. Homogenates were prepared from biopsies of visceral adipose tissue. The level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocytic chemoattractant protein-1 (MCP-1) was determined in blood and obtained homogenates of adipose tissue by multiplex analysis.Results. A weak positive relationship was found between serum IL-6 levels and adipose tissue. A weak positive relationship was found between IL-6 visceral adipose tissue and the VAI index, as well as between MCP-1 visceral adipose tissue and the LAP and VAI indices. The level of MCP-1 in visceral adipose tissue is directly associated with the LAP insulin resistance index (6,255 [1,648; 10,862], p = 0.008), TNF-α – with the VAI insulin resistance index (1,076 [0.335; 1,817], p = 0.005).Conclusion. Of the proinflammatory cytokines we studied, an association with insulin resistance was shown for MCP-1 and TNF-α visceral adipose tissue. At the same time, MCP-1 is directly associated with the LAP index, and TNF-α is directly associated with the VAI index.
The aim of the study was to investigate differences in the content of unsaturated fatty acids (UFA) in blood plasma in men living of rural areas of the Novosibirsk region, depending on their alcohol status. Materials and methods: as part of a single-stage epidemiological study in the Novosibirsk region, rural residents (men) aged 60.04±10.55 (from 35 to 74 years) were examined. The alcohol status of the participants was determined by means of a questionnaire. The number of different alcoholic beverages was recalculated in doses of pure alcohol. All study participants were divided into three groups based on alcohol consumption per week: group 1 — low alcohol consumption (LC); group 2 — moderate alcohol consumption (MC); group 3 — high alcohol consumption (HC). The levels of omega-3, -6, and -9 UFA in blood plasma were determined by high-performance liquid chromatography. Results: It was found that the group of men with HC had higher concentrations of omega-3 alpha-linolenic acid (p=0,041) and omega-6 digomo-gamma-linolenic (p=0,002), docosatetraenoic (p=0,017), docosapentaenoic (p=0,023) UFA in blood, compared with group of men with LC. Conclusions: In the study, we found statistically significant differences in blood concentrations of alpha-linolenic acid, digomo-gammalinolenic acid, docosathetraenoic acid, and docosapentaenoic acid unsaturated fatty acids were obtained in men aged 35-74 years living in rural areas of the Novosibirsk region, depending on alcohol consumption.
Aim. To identify associations of visceral adipose tissue adipokines with metabolic disorders in abdominal obesity.Materials and methods. The study included 101 individuals aged 25–65 years (51 men). For all patients, questionnaires were completed, anthropometric measurements and 3 measurements of blood pressure were performed, fasting blood was sampled, and biopsies of visceral adipose tissue were collected during elective surgery. The parameters of the lipid profile and glucose levels were determined in the blood by enzymatic methods. Homogenates from biopsies of visceral adipose tissue were prepared. The blood levels of adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor type 1 (PAI-1), and resistin were measured, and homogenates of adipose tissue were obtained by the multiplex analysis. Sex hormone levels in the blood of all patients (estradiol in women, testosterone in men) were determined by the enzyme-linked immunosorbent assay (ELISA) kits.Results. We identified correlations between serum levels of adipsin and adipose tissue and between adipsin from adipose tissue and PAI-1 in the blood serum. A weak negative relationship was found between the level of adiponectin and waist circumference, body mass index, and insulin resistance indices: triglyceride glucose index (TyG), lipid accumulation product (LAP), and visceral adiposity index (VAI). The level of adiponectin in visceral adipose tissue was inversely correlated with overweight in males and in the 45–65 age group. The level of resistin in visceral adipose tissue showed an inverse correlation with diastolic blood pressure, which persisted in the age group of 25–44 years.Conclusion. Of the studied adipokines, a relationship with cardiometabolic parameters was shown for adiponectin and resistin. At the same time, adiponectin was inversely correlated with overweight in the group of men and in the age group of 45–65 years, while resistin was inversely correlated with diastolic blood pressure in the age group of 25–44 years.
Among the various factors potentially involved in the pathogenesis of cardiovascular diseases, arterial hypertension (HTN), in the structure of which the proportion of young people increases, is still the most common risk factor for the development of serious cardiovascular complications. The development of structural and functional disorders associated with HTN is accompanied by an increase or decrease in markers of metabolic disorders. Objective. Тo study the prevalence of HTN in young people of working age and childbearing age, depending on the levels of metabolic hormones. Design and methods. The study included 1,340 people from the Novosibirsk population sample aged 25–44 years. HTN was diagnosed in case of the average systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, insulin, pancreatic polypeptide (PP), and peptide YY (PYY) were determined by multiplex analysis. Results. In the quartile with the highest values of amylin, C-peptide, GIP, GLP-1 and PP, the prevalence of HTN is significantly higher compared to Q1. In the group of HTN patients, the levels of amylin, C-peptide, ghrelin, GIP, GLP-1, insulin and PP were 2,4 (p < 0,0001), 1,4 (p < 0,0001), 1,3 (p = 0,001), 1,3 (p = 0,003), 1,6 (p = 0,001), 1,2 (p = 0,002) and 1,4 (p = 0,006) times higher, respectively, in comparison with persons without HTN. Conclusions. The prevalence of HTN is associated with high values of amylin, ghrelin, glucagon, insulin and C-peptide. The chance of HTN increases starting from the second quartile of amylin and increases with each quartile.
Aim. To study the associations of the levels of metabolic and inflammatory molecules and the severity of postCOVID syndrome (PCS) in COVID-19 convalescents.Materials and methods. The observational cross-sectional study included 270 individuals aged 18–84 who were COVID-19 convalescents, including 191 patients with PCS of whom 97 patients had mild PCS and 94 had moderate PCS. Serum concentrations of metabolic and inflammatory molecules were determined using enzymelinked immunosorbent assay (ELISA), including: alpha interferon (IFN-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), insulin, C-peptide, and high-sensitivity C-reactive protein (hs-CRP).Results. In COVID-19 convalescents with PCS of varying severity, the level of IL-6 was 1.3 times higher than in individuals without PCS. Among men with PCS, the levels of IL-6, MCP-1, and hs-CRP were 1.5, 1.2 and 1.9 times higher, respectively, compared with men without PCS. In men with moderate PCS, the level of IL-6 was 1.9 times higher and hs-CRP was 1.7 times higher than in men without PCS. The risk of having moderate PCS in COVID-19 convalescents was directly associated with the concentration of C-peptide in the blood. In men, the risk of having PCS was directly associated with the concentration of hs-CRP in the blood.Conclusion. In COVID-19 convalescents, the risk of having moderate PCS is directly associated with the level of C-peptide in the blood. In men, the risk of having PCS is directly associated with the level of hs-CRP in the blood.
BACKGROUND: Diabetes mellitus and obesity are two closely related diseases that are a global public health problem. Obesity is characterized by an increase in the volume of adipose tissue and a change in the production and function of adipocytokines, which leads to a violation of the regulation of insulin sensitivity and glucose metabolism, contributing to the development of insulin resistance and diabetic pathology.AIM: The aim of this study was to evaluate the concentrations of individual adipocytokines and metabolic hormones in patients with DM2 and without diabetes, depending on the presence/absence of abdominal obesity (AO).MATERIALS AND METHODS: A single-center observational cross-sectional study was conducted. A population subsample of men and women aged 25–44 years was examined. Socio-demographic data were collected, anthropometric measurements were performed. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, were determined in blood serum by multiplex analysis using a set of reagents Human Metabolic Hormone V3 (USA) and Human Adipokine Panel 1 (USA) on a Luminex MAGPIX flow fluorimeter (USA). interleukin 6, insulin, leptin, monocytic chemotactic factor 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor-1 (PAI-1) and resistin.RESULTS: The study included 105 people. The main group consisted of 35 people with diabetes mellitus, 11 of them without AO and 24 with AO, the control group consisted of 70 people without diabetes mellitus (35 people with AO and 35 without AO), comparable in gender and age with the main group. In individuals with abdominal obesity, regardless of the presence of type 2 diabetes mellitus, the levels of C-peptide, GLP-1, insulin, leptin and TNF-alpha are higher than in individuals without abdominal obesity. The chance of having diabetes mellitus and AO is associated with an increase in leptin levels (OR=1.367, 95% CI: 1.050–1.779, p=0.020).CONCLUSION: The results of our study show that the indicators of the adipocytokine profile differ significantly in individuals with the presence/absence of abdominal obesity. According to our data, leptin makes the greatest contribution to the development of SD2 against the background of AO. Further research is needed to identify causal relationships and determine whether treatment that regulates adipocytokine levels can help in personalized approaches to the prevention and treatment of type 2 diabetes mellitus.
Aim. To study the associations of abdominal obesity (AO), levels of biochemical markers of chronic and acute inflammation, and post-COVID syndrome (PCS) in coronavirus disease 2019 (COVID-19) convalescents.Material and methods. The cross-sectional observational study included 166 people aged 18-84 (44,6% men) who were COVID-19 convalescents. In all patients, medical history and anthropometric data were collected. AO was defined as waist circumference >80 cm in women and >94 cm in men. In the blood serum, the concentrations of following biochemical markers of chronic and acute inflammation were determined by the enzyme immunoassay method: interferon alpha, interleukins (IL) 1 beta (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), insulin, C-peptide, high-sensitivity C-reactive protein (hsCRP).Results. COVID-19 convalescents with PCS and AO had significantly higher levels of IL-6 (3,13 [2,26;4,98] and 1,74 [1,10;3,04] pg/ml, p<0,0001, respectively) and hsCRP (3,83 [2,42;10,16] and 2,34 [0,70;5,79] mg/l, p=0,028, respectively) than without AO. Insulin and C-peptide demonstrated significant differences in COVID-19 convalescents with AO regardless of PCS. Multivariate logistic regression analysis showed that the odds of having AO in COVID-19 convalescents with PCS increased by 1,6 times with an increase in blood IL-6 by 1 pg/ml (odds ratio (OR) 1,581, 95% confidence interval (CI): 1,001-2,416; p=0,047) and by 1,2 times with an increase in blood insulin by 1 pg/ml (OR 1,168, 95% CI: 1,015-1,343; p=0,030). AO in men with PCS is associated with the concentration of IL-6 (OR 1,943, 95% CI: 1,018-3,709; p=0,044) and IL-1β (OR 0,591, 95% CI: 0,362-0,967; p=0,036). PCS in women with AO and cardiovascular diseases is associated with the level of MCP-1 (OR 0,991, 95% CI: 0,983-0,999; p=0,035).Conclusion. In COVID-19 convalescents with PCS, the AO probability is associated with an increase in blood IL-6 and insulin. In men, the AO probability is associated with an increase in IL-6 and a decrease in IL-1β. In women with AO and a history of cardiovascular diseases, PCS is associated with the level of MCP-1 in the blood.
Aim . To analyze the results of the GastroPanel and GastroScreen-3 tests over a 15-year follow-up and determine the incidence of autoimmune gastritis (AIG) in clinical practice and in a random sample of Novosibirsk residents. Materials and methods . Biomarkers were analyzed in two groups: 1,742 people, average age of 50.0 ± 13.53 years (GastroPanel test, Biohit Oy, Finland), and 170 people, average age of 53.8 ± 12.89 years (GastroScreen-3 test, Vector-Best, Russia), from 2007 to 2022. The AIG incidence was calculated in current clinical practice and in a random sample of Novosibirsk residents aged 45–69 years. The PGI level of 160 µg / l was taken as the upper limit of normal, PGI of 31–50 µg / l indicated moderate atrophy, PGI < 30 µg / l and the PGI / PGII ratio ≤ 3 indicated severe gastric fundus atrophy. AIG was considered at PGI ≤ 10.1 μg / l, the PGI / PGI ratio ≤ 1.3, and gastrin-17 ≥ 42.4 pmol / l (GastroPanel) and at PGI ≤ 16.8 μg / l and the PGI / PGII ratio ≤ 1.5 (GastroScreen-3). The H. pylori IgG level > 42 EIU was considered to be positive. Antibodies to CagA protein were determined using the HelicoBest Antibody test (Vector-Best, Novosibirsk). Results . Serological signs of severe and moderate gastric fundus atrophy were detected in 10 and 9.4% (GastroPanel test) and in 13.3 and 7% (GastroScreen-3 test) of those examined, respectively. Signs of multifocal atrophy were found in 0.7% of cases. Antibodies to H. pylori were detected in 57.7%, CagA+ strain – in 56.1% of cases. Peptic ulcer disease (PGI ≥160 µg / l) was found in 15.3% (GastroPanel test) and 10% (GastroScreen-3 test) of the examined. According to the GastroPanel and GastroScreen-3 tests, the incidence of AIG was 1.6% in a random sample and 2.6 and 3.5% in current clinical practice, respectively. Conclusion . Twenty percent of the examined persons were at risk of developing gastric cancer and 10–15% had peptic ulcer disease, which requires further examination. The incidence of AIG in different study groups based on serological screening was 1.6–3.5%.
Aim. To study the levels of adipocytokines and their associations with stable and unstable atherosclerotic plaques in patients with a high triglyceride – glucose (TyG) index.Materials and methods. The study included 109 men aged 38–79 years (mean age 62.28 ± 8.19 years) with atherosclerosis hospitalized for coronary artery bypass grafting (CABG). After microscopy of the intima – media layer, the type of atherosclerotic plaque was determined: stable / unstable. The TyG index ≥ 4.49 was considered as high. Fifty-eight (60%) men had stable plaques in the CA (28 (56%) of them had TyG ≥ 4.49); 39 (40%) men had unstable plaques in the CA (15 (39%) had TyG ≥ 4.49). Blood adipocytokine level was studied using the multiplex assay and the Human Metabolic Hormone Panel V3.Results. The final analysis included 97 patients. The level of glucose-dependent insulinotropic polypeptide (GIP) was 1.53 times greater in patients with TyG ≥ 4.49 (34.16 [18.71; 54.98] vs. 22.34 [15.02; 34.77], p = 0.004). In patients with TyG < 4.49, the adipsin level was 1.2 times higher in patients with unstable plaques than in patients with stable ones. In patients with stable plaques and TyG ≥ 4.49, the GIP level was 1.88 times higher than in patients with TyG < 4.49 (42.13 [25.34; 68.95] vs. 22.39 [17.00; 28.60], p = 0.003). In patients with unstable plaques and TyG ≥ 4.49, the level of peptide tyrosine – tyrosine (PYY) was 1.46 times greater than in patients with TyG < 4.49 (46.14 [30.49; 70.66] vs. 31.53 [24.71; 43.01], p = 0.048).Conclusion. Men with atherosclerosis and TyG ≥ 4.49 had higher blood levels of GIP and PYY. Blood adipsin levels were higher in patients with unstable plaques without insulin resistance.
Cardiovascular diseases (CVDs) are one of the world's main causes of mortality. The role of matrix metalloproteinases (MMPs) as markers of CVD complications has been actively discussed in recent years. It has been proven that a high level of MMPs contributes to the development of unstable plaque, aggravating a patient's prognosis. Being an independent risk factor, obesity also results in complications of cardiovascular diseases. Studies on the effect an increase in the body mass index and adipose tissue hormones on the level of MMPs have begun to appear. Results from clinical and experimental studies over the last 5 years devoted to studying matrix metalloproteinases are presented here. The role of MMPs in the pathogenesis of atherosclerosis is reflected. MMPs are considered biomarkers of the development of adverse cardiovascular events. Results from studies on the effect obesity has on the level of MMPs are also presented here. A search was performed for articles in the PubMed, Google Scholar, and Elibrary databases for the period from 2018 to 2023 using the keywords metalloproteinases and atherosclerosis, metalloproteinases and obesity, and the connection between atherosclerosis and obesity separately for each type of MMP.
Aim. To study the effect of extended-release (XR) metformin on humoral cardiometabolic markers and lipid peroxidation parameters in patients with heart failure with preserved ejection fraction (HFpEF), prediabetes and abdominal obesity (AO). Material and methods. The study included 64 people (men – 50%, median age – 58 [55,25; 59,75] years) with HFpEF, prediabetes and AO. All patients (groups A and B) received optimal therapy for HFpEF. In group A (n=32), metformin XR 1000-1500 mg/day was additionally prescribed. A general clinical examination was carried out, determining the level of soluble interleukin 33 receptor (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), the initial level of malondialdehyde (MDA) in low-density lipoproteins (LDL) and their resistance to oxidation with copper ions initially and after 6 months. Results. In group A, a decrease in NT-proBNP by 3,7% (p <0,001) was recorded. In group B, NT-proBNP values increased by 2,7% (p=0,013) compared to baseline levels. The decrease in NT-proBNP in the metformin group was accompanied by a decrease in hsCRP levels by 31% (p<0,001). No changes in sST2 concentration were demonstrated in either group. The level of MDA in LDL after 6-month metformin therapy became lower by 20% (p=0,002) relative to the initial value. When assessing the resistance to LDL oxidation with copper ions, the MDA content did not differ from the initial value. In group B, the initial MDA content in LDL increased by 3,7% (p=0,002) and after incubation with copper ions increased by 31,8% (p<0,001). Conclusion. In patients with prediabetes, HFpEF and AO, 6-month metformin XR + optimal HFpEF therapy was associated with a decrease in NT-proBNP, as well as the severity of oxidative stress in the form of a decrease in the concentration of MDA in LDL and the serum level of hsCRP.
Aim To study metabolic molecules (adiponectin, adipsin, resistin, glucagon-like peptide-1 (GLP-1), glucagon, secretin) of adipose tissue in atherosclerotic plaques (AP) and their associations with AP instability in men with coronary atherosclerosis. Material and methods Metabolic molecules (adipocytokines and metabolic hormones) of adipose tissue can act as enzymes, hormones or growth factors in modulating insulin resistance and lipid and glucose metabolism and indirectly influence the course of the atherosclerotic process. This study included 48 men from whom 139 coronary artery (CA) samples were collected during coronary artery bypass grafting, after obtaining the informed consent. According to the histological conclusion, 84 (60.4 %) CA plaques were stable, 44 (31.7 %) were unstable, and 11 histological samples had a conditionally unchanged CA intima (7.9 %). The concentrations of adiponectin, adipsin, resistin, GLP-1, glucagon, and secretin were measured in AP homogenates by multiplex analysis using the Human Metabolic Hormone V3 panel (MILLIPLEX, Germany). During the study, demographic and anthropometric characteristics, medical history, and presence of chronic diseases were recorded. Results The glucagon concentration in the conditionally unchanged intima was 16.7 % lower and in the fragments of unstable atherosclerotic plaques 41.2 % lower than in fragments of stable APs. However, the glucagon concentration in stable APs was 28 % higher than in unstable APs. The secretin concentration in the conditionally unchanged intima was also lower than in stable APs by 41.2 %, while in stable APs, the secretin concentration was 20 % higher than in unstable APs. The adiponectin concentrations were directly correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations (r=0.286; p=0.002), while the secretin concentrations were inversely correlated with serum HDL-C concentrations (r= -0.199; p=0.038). The probability of having an unstable AP (in relation to conditionally unchanged intima) increases by 35.8 % with an increase in the AP glucagon concentration by 1 pg / mg protein. The probability of having a stable AP (in relation to unchanged intima) increases by 29.4 % with an increase in the AP glucagon concentration by 1 pg / mg protein and by 10.1 % with an increase in the AP secretin concentration by 1 pg / mg protein. Conclusion The AP adiponectin concentration directly correlates and the AP secretin concentration inversely correlates with the serum concentration of HDL-C. The presence of both stable and unstable APs is directly associated with the AP glucagon concentration in men with coronary atherosclerosis. The AP secretin concentration is directly associated with plaque stability in men with coronary atherosclerosis. Further thorough study of the identified markers in atherosclerotic lesions will allow using them as potential targets for therapy.
BACKGROUND: The people with an excessive amount of adipose tissue have elevated levels of free fatty acids (FFA) in the blood, which ultimately leads to disorders of lipid metabolism and insulin resistance, which are the main factors in the development of diabetes mellitus.AIM: To study the content of FFA in blood plasma, as well as their association with body weight in men.MATERIALS AND METHODS: A single-center observational one-stage study was conducted. The sample was formed by a random representative method, comparable by sex and age. The levels of FFA were determined in the blood plasma by high-performance liquid chromatography with mass spectrometry.RESULTS: The study included 250 men. The selected participants were divided into groups according to their body mass index (BMI): Group 1 — 62 people with BMI≤24.9 kg/m2, Group 2 — 101 people with BMI 25.0–29.9 kg/m2, Group 3 — 87 people with BMI≥30.0 kg/m2. Obese men were divided into: Group 4 — 62 people with BMI 30.0–34.9 kg/m2, Group 5 — 19 people with BMI 35.0–39.9 kg/m2, Group 6 — 6 people with BMI≥40.0 kg/m2.The content of docosatetraenoic acid was higher in groups 2 (p=0.002) and 5 (p=0.003), when compared with group 1. The content of gamma-linolenic acid was higher in group 3 than in group 1 (p=0.041). Concentration of oleic; linoleic; dihomo-gamma-linolenic; midic; arachidonic; eicosapentaenoic acids were higher in group 5 than in group 1 (p=0.007, p=0.023, p=0.004, p=0.019, p=0.006, p=0.001, respectively), and also than in group 2 (p=0.006, p=0.017, p=0.007, p=0.007, p=0.008, p=0.001, respectively). The content of nervonic acid is higher in groups 1 (p=0.029) and 2 (p=0.012) than in group 4. Obesity is associated with increased levels of gamma-linolenic (1.030, 1.006–1.056, p=0.015) and eicosapentaenoic acids (1.061, 1.000–1.125, p=0.045), and a decrease in the level of nervonic acid (0.953, 0.913–0.994, p=0.027).CONCLUSION: The FFA levels of blood plasma is significantly different in men with normal body weight and the presence of obesity. The content of oleic, gamma-linolenic, midic, digomo-gamma-linolenic, arachidonic, docosatetraenoic and eicosapentaenoic acids was significantly higher in men with grade 2 obesity. An increase in the level of gamma-linolenic and eicosapentaenoic acids, and a decrease in the level of nervonic acid are associated with obesity, regardless of the age.