Modern biomarkers of oxidative stress estimated by immuno-enzymal analysis

The literature review presents the results of studies carried out in the world over the past years, devoted to the study of factors and markers of oxidative stress in the development of therapeutic diseases, especially cardiovascular diseases. The article describes the results of studies using enzyme immunoassay of such biomarkers of oxidative stress as glutathione peroxidase, superoxide dismutase, oxidatively modified low density lipoproteins, carbonylated proteins, as well as the general antioxidant capacity of the blood

Proinflammatory adipokines and cytokines in abdominal obesity as a factor in the development of atherosclerosis and renal pathology

In recent decades, there has been an increase in the prevalence of overweight and obesity. Obesity has become an underestimated pandemic and a public health threat around the world. Adipose tissue is positioned as an endocrine organ that secretes a wide range of pro-inflammatory cytokines and adipokines, inducing a state of chronic subinflammation. The results of epidemiological studies over the past 30 years have also shown that visceral adipose tissue is an independent risk factor for the development of atherosclerosis, cardiometabolic diseases and chronic kidney disease. We performed a systematic review to summarize important aspects of the state of chronic subinflammation in the context of its effect on the decrease in glomerular filtration rate and the development of chronic kidney disease. The review deals with the etiology and pathogenesis of obesity, the hormonal profile of adipose tissue, the molecular mechanisms of the effect of pro-inflammatory cytokines and adipokines on the kidneys, and the pathophysiology of renal diseases. Information on the topic from publications based on the Pubmed database has been used

Тhe prevalence of metabolically healthy obesity: data from the epidemiological survey in of Novosibirsk

Background: Obesity is associated with numerous metabolic complications, such as type 2 diabetes mellitus (DM2), dyslipidemia, arterial hypertension (AH), cardiovascular diseases and some forms of cancer. Nevertheless, the literature describes a group of obese individuals who are more resistant to the development of metabolic disorders. At present, this phenomenon is known as "Metabolically healthy obesity", "metabolically healthy obesity" (MZO). Despite the presence of excess weight or obesity, a favorable metabolic profile can be observed in this cohort of patients, characterized by preserved insulin sensitivity, absence of arterial hypertension, normal lipid, hormonal profile, absence of inflammation and unchanged hepatic transaminases. Aims: To study the prevalence of metabolically healthy obesity (MHO) and its characteristics in men and women at the age of 45–69 years in Novosibirsk. Materials and methods: To study covered 3197 persons from the base of the international project HAPPIE. They had a body mass index (BMI ≥ 30 kg/m²). «Metabolically healthy obesity» was determined as obesity (BMI ≥ 30 kg/m², with 2 and fewer components of metabolic syndrome (MS) by criteria NCEP ATP III, 2001. Statistical analisys SPSS-13. Results: The prevalence of metabolic healthy obesity (MHO) was 42% (38% for men and 43% for women). The examined people with MHO have reliably more favorable average level of TG, HDL-cholesterol, indicators of blood glucose, systolic arterial pressure and diastolic arterial pressure and less waist circumference. In the groups withMHO and MS abdominal obesity is common in men at 95 and 71%, in women at 99 and 90%; hyperTG – in men at 74 and 9%, in women at 72 and 5,5%; lower level HDL-cholesterol in 16 and 1% for men, and in 44,5% and 3% for women; AP in 96 and 77% and 94 and 71% in men and women respectively, the frequency fasting of hyperglycaemia 77 and 21% in men and 60 and 5% in women was markedly different. According to the data obtained by us, the frequency in the sample is high and amounted to 42%. In the subgroup the most commonly found is the MHO phenotype – 53%, than in the men -38%, р <0,001 Conclusions: According to our data, the frequency of metabolic healthy obesity in the sample is high and amounted to 42%. In the female subgroup, a metabolically healthy phenotype is more common 43% than in the male 38%, p <0.001. Metabolically healthy obese individuals are characterized by a significantly lower incidence of fasting hyperglycaemia and dyslipidemia

Why does Russia have such high cardiovascular mortality rates? Comparisons of blood-based biomarkers with Norway implicate non-ischaemic cardiac damage.

BACKGROUND: Russia has one of the highest rates of mortality from cardiovascular disease (CVD). At age 35-69 years, they are eight times higher than in neighbouring Norway. Comparing profiles of blood-based CVD biomarkers between these two populations can help identify reasons for this substantial difference in risk. METHODS: We compared age-standardised mean levels of CVD biomarkers for men and women aged 40-69 years measured in two cross-sectional population-based studies: Know Your Heart (KYH) (Russia, 2015-2018; n=4046) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015-2018; n=17 646). A laboratory calibration study was performed to account for inter-laboratory differences. RESULTS: Levels of total, low-density lipoprotein-, high-density lipoprotein-cholesterol and triglycerides were comparable in KYH and Tromsø 7 studies. N-terminal pro-b-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hsCRP) were higher in KYH compared with Tromsø 7 (NT-proBNP was higher by 54.1% (95% CI 41.5% to 67.8%) in men and by 30.8% (95% CI 22.9% to 39.2%) in women; hs-cTnT-by 42.4% (95% CI 36.1% to 49.0%) in men and by 68.1% (95% CI 62.4% to 73.9%) in women; hsCRP-by 33.3% (95% CI 26.1% to 40.8%) in men and by 35.6% (95% CI 29.0% to 42.6%) in women). Exclusion of participants with pre-existing coronary heart disease (279 men and 282 women) had no substantive effect. CONCLUSIONS: Differences in cholesterol fractions cannot explain the difference in CVD mortality rate between Russia and Norway. A non-ischemic pathway to the cardiac damage reflected by raised NT-proBNP and hs-cTnT is likely to contribute to high CVD mortality in Russia

АССОЦИАЦИИ УРОВНЯ В КРОВИ ХОЛЕСТЕРИНА ЛИПОПРОТЕИНОВ НИЗКОЙ ПЛОТНОСТИ И БИОМОЛЕКУЛ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ У ЛЮДЕЙ 25–44 ЛЕТ

Highlights The study is devoted to the analysis of metabolic hormones and their relationship with the main risk factors for cardiovascular diseases, in particular, elevated levels of low-density lipoprotein cholesterol. The study included people under the age of 45 with active hormones. AbstractAim. To assess the relationship between the levels of LDL and metabolic hormones reflecting metabolic disorders in young people.Methods. The study included 305 people. The group 1 included 146 people with an LDL level of <2.1 mmol/L, the group 2 included 159 people with an LDL level of ≥4.2 mmol/L. Serum total cholesterol (TC), triglycerides, HDL and glucose concentrations were determined by enzymatic method using Thermo Fisher Scientific kits (Finland) on a 30i KonelabPrime clinical chemistry analyzer. The calculation of concentrations of LDL was carried out according to the Friedwald formula. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, peptide YY, tumor necrosis factor alpha were determined by multiplex analysis using the Human Metabolic Hormone V3 (MILLIPLEX) panel on a Luminex MAGPIX flow fluorimeter.Results. In the group of patients with LDL ≥4.2 mmol/L, fasting glucose disorders were much more prevalent, the average BMI (p = 0,0001) was higher, and arterial hypertension was twice as frequent (24.8% vs. 11.6%, p = 0.003) compared with the group 1. The levels of triglycerides, TC, and glucose were higher, whereas HDL level was lower in the group 2(p = 0,0001). In patients with LDL ≥4.2 mmol/L, the values of HOMA-IR and the occurrence of IR (83.8%) according to the HOMA-IR were higher compared with the group with LDL <2.1 mmol/L (p = 0,0001). Statistically significant differences in the levels of the studied indicators between the groups 1 and 2 were obtained for C-peptide, GLP-1, insulin and leptin. The relative chance of having LDL≥4.2 mmol/L is associated with an increase in the level of C-peptide (OR = 2.042, 95% CI 1.209–3.449, p = 0.008) and a decrease in the level of GLP-1 (OR = 0.997, 95% CI 0.996–0.999, p = 0.001).Conclusion. An increase in LDL levels in young people is associated with disorders of lipid and carbohydrate metabolism. These data are confirmed by changes in the serum metabolic markers that characterize metabolic disorders in the human body.Основные положенияИсследование посвящено изучению метаболических гормонов и их связи с основными факторами риска сердечно-сосудистых заболеваний, в частности с повышенным уровнем холестерина липопротеинов низкой плотности. В исследование включены люди в возрасте до 45 лет с активным гормональным статусом. АннотацияЦель. Оценить связь между уровнем холестерина липопротеинов низкой плотности (ХС-ЛНП) и метаболическими гормонами, отражающих нарушения обменных процессов у молодых людей.Материалы и методы. В исследование включено 305 человек. В первую группу вошло 146 человек с уровнем ХС-ЛНП <2,1 ммоль/л, во вторую группу – 159 человек с уровнем ХС-ЛНП ≥4,2 ммоль/л. Содержание общего холестерина, триглицеридов, холестерина липопротеинов высокой плотности и глюкозы в сыворотке крови определяли энзиматическим методом с использованием наборов Thermo Fisher Scientific (Финляндия) на биохимическом анализаторе Konelab Prime 30i. Вычисление значений концентрации ХС-ЛНП проводили по формуле Фридвальда. Методом мультиплексного анализа с применением панели Human Metabolic Hormone V3 (MILLIPLEX; EMD Millipore Corp., Германия) на проточном флуориметре Luminex MAGPIX (Luminex Corp., США) определяли уровни амилина, С-пептида, грелина, глюкозозависимого инсулинотропного полипептида, глюкагоноподобного пептида 1, глюкагона, интерлейкина 6, инсулина, лептина, моноцитарного хемотаксического фактора 1, панкреатического полипептида, пептида YY, фактора некроза опухолей альфа.Результаты. В группе лиц с уровнем ХС-ЛНП ≥4,2 ммоль/л зарегистрирована более высокая распространенность нарушений уровня глюкозы натощак, в два раза чаще по сравнению с первой группой чаще встречалась артериальная гипертензия (24,8 против 11,6%, p = 0,003) и определены более высокие средние значения индекса массы тела (p = 0,0001). Уровни триглицеридов, общего холестерина, глюкозы плазмы были выше, а показатель ХС-ЛВП ниже у лиц второй группы (p˂0,0001). У пациентов с уровнем ХС-ЛНП ≥4,2 ммоль/л как само значение индекса НОМА-IR, так и встречаемость инсулинорезистентности (83, 8%) в соответствии с индексом НОМА-IR были выше в сравнении с группой лиц с ХС-ЛНП <2,1 ммоль/л (p˂0,0001). Статистически значимые отличия в уровнях изучаемых показателей между группами получены для С-пептида, глюкагоноподобного пептида 1, инсулина и лептина. Относительный шанс наличия ХС-ЛНП ≥4,2 ммоль/л ассоциирован с повышением уровня С-пептида (отношение шансов 2,042, 95% доверительный интервал 1,209–3,449, p = 0,008) и уменьшением уровня глюкагоноподобного пептида 1 (отношение шансов 0,997, 95% доверительный интервал 0,996–0,999, p = 0,001).Заключение. Повышение уровня ХС-ЛНП у молодых людей ассоциировано с нарушениями не только липидного, но и углеводного обмена. Эти данные подтверждает изменение в крови метаболических маркеров, характеризующих нарушение обменных процессов в организме человека

АССОЦИАЦИИ БИОМОЛЕКУЛ, СВЯЗАННЫХ С СЕКРЕТОРНОЙ АКТИВНОСТЬЮ ВИСЦЕРАЛЬНЫХ АДИПОЦИТОВ, С ЭЛЕКТРОФИЗИОЛОГИЧЕСКИМИ ПРИЗНАКАМИ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ МИОКАРДА У ЛИЦ ДО 45 ЛЕТ

Highlights ECG signs of metabolic cardiomyopathies in men aged 25–44 years, regardless of age and waist circumference, are directly associated with the serum adipsin concentration and inversely associated with the concentration of glucagon-like peptide 1 in the blood.ECG signs of metabolic cardiomyopathies in women aged 25–44 years are directly associated with the serum c-peptide concentration and inversely associated with the concentration of glucose-dependent insulinotropic polypeptide 1 in the blood. AbstractAim. To study the relationship between electrophysiological signs of metabolic cardiomyopathy (MC) and biomolecules associated with the secretory activity of visceral adipocytes in persons aged 25–44 years residing in Novosibirsk.Methods. The study included 1 198 subjects. A single-stage survey of a random sample of the 25–44-year-old population of Novosibirsk (49,7% men, 50,3% women) was conducted. During the examination, among other things, a resting 12-lead ECGs was recorded, and later the ECGs were classified according to Minnesota Code categories. Five ECG signs of MC were analysed: 1) ST-segment displaced above baseline (ST-segment elevation); 2) ST-segment displaced below baseline (ST-segment depression); 3) T wave changes; 4) TV1>TV6 patterns and 5) ECG signs of left ventricular hypertrophy. Serum concentrations of biomolecules associated with the secretory activity of visceral adipocytes were determined by multiplex analysis.Results. The results of multivariate logistic regression analysis showed that the ECG signs of MC in men aged 25–44 years, regardless of age and waist circumference, are directly associated with the serum adipsin concentration (Exp B 1,039, 95% CI 1,002–1,077, p = 0.039) and inversely associated with the concentration of glucagon-like peptide 1 in the blood (Exp B 0.999, 95% CI 0.998–1,000, p = 0.042). ECG signs of MC in women aged 25–44 years are directly associated with the serum peptide concentration (Exp B 1,439, 95% CI 1,082–1,915, p = 0.012) and inversely associated with the concentration of glucose-dependent insulinotropic polypeptide in the blood (Exp B 0.986, 95% CI 0.978–0.995, p = 0.001).Conclusion. The results obtained reflect the significant influence of these biomolecules associated with the secretory activity of visceral adipocytes on the occurrence of ECG signs of MC in young people aged 25–44 years.Основные положенияЭКГ-признаки метаболических нарушений миокарда у мужчин 25–44 лет независимо от возраста и окружности талии прямо ассоциированы с концентрацией в крови адипсина и обратно – с концентрацией глюкагоноподобного пептида 1.ЭКГ-признаки метаболических нарушений миокарда у женщин 25–44 лет прямо ассоциированы с концентрацией в крови C-пептида и обратно – с концентрацией глюкозозависимого инсулинотропного полипептида 1. Цель. Изучить ассоциации электрофизиологических признаков метаболических нарушений миокарда (МНМ) с биомолекулами, связанными с секреторной активностью висцеральных адипоцитов, у лиц 25–44 лет, проживающих в Новосибирске.Материалы и методы. Проведено одномоментное обследование случайной выборки населения Новосибирска в возрасте 25–44 лет (1 198 человек, 49,7% мужчин и 50,3% женщин). При обследовании в том числе проведена запись электрокардиограммы (ЭКГ) в покое в 12 стандартных отведениях с последующим кодированием по Миннесотскому коду. Проанализированы пять ЭКГ-признаков МНМ: смещение сегмента ST выше изолинии, депрессия сегмента ST ниже изолинии, изменения зубца Т, синдром TV1>TV6 и ЭКГ-признаки гипертрофии левого желудочка. В крови обследованных методом мультиплексного анализа определены концентрации биомолекул, ассоциированных с секреторной активностью висцеральных адипоцитов.Результаты. Результаты многофакторного логистического регрессионного анализа показали, что ЭКГ-признаки МНМ у мужчин 25–44 лет независимо от возраста и окружности талии прямо ассоциированы с концентрацией в крови адипсина (Exp B 1,039, 95% доверительный интервал (ДИ) 1,002–1,077; p = 0,039) и обратно – с концентрацией в крови глюкагоноподобного пептида 1 (Exp B 0,999, 95% ДИ 0,998–1,000; p = 0,042). Наличие ЭКГ-признаков МНМ у женщин 25–44 лет прямо ассоциировано с концентрацией в крови С-пептида (Exp B 1,439, 95% ДИ 1,082–1,915; p = 0,012) и обратно – с концентрацией в крови глюкозозависимого инсулинотропного полипептида (Exp B 0,986, 95% ДИ 0,978–0,995; p = 0,001).Заключение. Полученные результаты отражают значимое влияние биомолекул, ассоциированных с секреторной активностью висцеральных адипоцитов, на возникновение у людей 25–44 лет ЭКГ-признаков МНМ

The Blood Cytokine Profile of Young People with Early Ischemic Heart Disease Comorbid with Abdominal Obesity

Objective: The aim was to study the blood cytokine/chemokine profile of 25–44-year-old people with early ischemic heart disease (IHD) comorbid with abdominal obesity (AO). Methods: A cross-sectional medical examination of subjects in Novosibirsk, Russia, was conducted after random sampling of the above age group. A total of 1457 subjects, 804 females and 653 males, were analyzed. The epidemiological diagnosis of IHD was made in accordance with 17 validated and functional criteria, employing exercise ECG for confirmation. Simultaneous quantitative analyses of 41 cytokines/chemokines in blood serum were performed by a multiplex assay using the HCYTMAG-60K-PX41 panel (MILLIPLEX MAP) on a Luminex 20 MAGPIX flow cytometer, with additional ELISA testing. Results: Flt3 ligand, GM-CSF, and MCP-1 were significantly associated with the relative risk of early IHD. In the presence of AO, GM-CSF, MCP-1 and IL-4 also significantly correlated with the relative risk of early IHD. By univariate regression analysis, the relative risk of early IHD was associated with lowered blood concentrations of Flt3 ligand, whereas the relative risk of early IHD in the presence of AO was associated with lowered blood concentrations of GM-CSF. Employing multivariable regression analysis, only lower blood levels of Flt3 ligand were associated with a relative risk of early IHD, whereas the relative risk of early IHD in the presence of AO was limited to lower levels of IL-4. Conclusion: Findings related to Flt3 ligand, GM-CSF, and IL-4 are consistent with the international literature. Results from the present study are partly confirmative and partly hypothesis generating

Calcification and atherosclerosis of the coronary arteries

Calcification is a very common phenomenon in the coronary arteries, which is part of the atherosclerotic process, and the degree of calcification can predict clinical outcomes in patients at high risk of coronary events. Both the degree of calcification and the patterns of its distribution are of prognostic importance, but the relationship of coronary artery calcification with atherosclerotic plaque instability is extremely complex and not fully understood. This article is devoted to the study of calcification markers and their influence on the development of atherosclerotic foci

Proteomic Studies of Blood and Vascular Wall in Atherosclerosis

The review is devoted to the analysis of literature data related to the role of proteomic studies in the study of atherosclerotic cardiovascular diseases. Diagnosis of patients with atherosclerotic plaques before clinical manifestations is an arduous task. The review presents the results of research on the new proteomic potential biomarkers of coronary heart disease, coronary atherosclerosis, acute coronary syndrome, myocardial infarction, carotid artery atherosclerosis. Also, the analysis of literature data on proteomic studies of the vascular wall was carried out. To assess the involvement of proteins in the pathological process of atherosclerosis, it is important to investigate the specific relationships between proteins in the arteries, expression and concentration of proteins. The development of proteomic technologies has made it possible to analyse the number of proteins associated with the development of the disease. Analysis of the proteomic profile of the vascular wall in atherosclerosis can help to detect possible diagnostically significant protein structures or potential biomarkers of the disease and develop novel approaches to the diagnosis of atherosclerosis and its complications