Associations of Adipocytokines and Early Renal Dysfunction in Young People on the Background of Dyslipidemia.

BACKGROUND: There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. MATERIALS AND METHODS: A population study was conducted in IIPM-Branch of IC&G SB RAS, in 2013-2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. RESULTS: Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. CONCLUSIONS: In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction.

Adipokine-Cytokine Profile in Patients with Unstable Atherosclerotic Plaques and Abdominal Obesity.

The goal of the research was to study the levels of adipokines and their associations with unstable atherosclerotic plaques in patients with coronary atherosclerosis and abdominal obesity (AO). METHODS: The study included 145 men aged 38-79 with atherosclerosis of the coronary arteries (CA) and stable angina pectoris II-III FC who were hospitalized for coronary bypass surgery (2011-2022). The final analysis included 116 patients. Notably, 70 men had stable plaques in the CA (of which 44.3% had AO), and 46 men had unstable plaques in the CA (of which 43.5% had AO). Adipocytokine levels were determined using multiplex analysis (Human Metabolic Hormone V3 panel). RESULTS: In the subgroup of patients with unstable plaques, patients with AO had a GLP-1 level that was 1.5 times higher and a lipocalin-2 level that was 2.1 times lower, respectively. GLP-1 is direct, and lipocalin-2 is inversely associated with AO in patients with unstable plaques. Among patients with AO, the level of lipocalin-2 in patients with unstable plaques was 2.2 times lower than in patients with stable plaques in the CA. The level of lipocalin-2 was inversely associated with the presence of unstable atherosclerotic plaques in the CA. CONCLUSION: GLP-1 is directly associated with AO in patients with unstable atherosclerotic plaques. Lipocalin-2 is inversely associated with unstable atherosclerotic plaques in patients with AO.

Adipokines, Metabolic Hormones and Their Associations with Abdominal Obesity against a Background of Hyper-LDL-C in Young People.

BACKGROUND: The present study was devoted to the search for possible associations between various adipokines/cytokines associated with the secretory activity of visceral adipocytes, elevated blood levels of LDL-C and abdominal obesity in people under 45 years. METHODS: A population sample of Novosibirsk residents (n = 1415) was divided into deciles based on the levels of LDL-C. The study included 158 people, 87 men and 71 women, who had serum LDL-C levels of ≥4.2 mmol/L. Abdominal obesity was found in 50% of people (54% men, 45% women). By multiplex analysis using the human metabolic hormone V3 panel and the human adipokine magnetic bead panel, levels of adipokines and inflammatory markers were determined on a Luminex MAGPIX flow fluorimeter. RESULTS: According to multivariate regression analysis (binary logistic regression), the most significant biomolecules, regardless of other factors, associated with the presence of AO against the background of hyper-LDL-C in young people were leptin (direct association) and lipocalin-2 (reverse association), leptin in young men (direct association), and leptin and TNF-alpha in women (direct association). CONCLUSIONS: Thus, in young people under 45 years with the presence of two important, potentially atherogenic risk factors-hyper-LDL-C and abdominal obesity-a complex of adipokines and metabolic hormones were associated with the presence of these diseases.

The Search for Associations of Serum Proteins with the Presence of Unstable Atherosclerotic Plaque in Coronary Atherosclerosis.

To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries of patients with coronary atherosclerosis using quantitative proteomics. The studies involved two groups of men with coronary atherosclerosis (group 1 (St) had only stable atherosclerotic plaques; group 2 (Ns) had only unstable atherosclerotic plaques, according to histological analysis of tissue samples); the average age of patients was 57.95 ± 7.22. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit. The identification of protein fractions was carried out by monitoring multiple reactions on a Q-TRAP 6500 mass spectrometer combined with a liquid chromatograph. Mass spectrometric identification revealed in serum samples from patients with unstable atherosclerotic plaques a reduced concentration of proteins in the blood: α-1-acid glycoprotein, α-1-antichymotrypsin, α-1-antitrypsin, ceruloplasmin, hemopexin, haptoglobin, apolipoprotein B-100, apolipoprotein L1, afamin and complement component (C3, C7, C9). Moreover, at the same time a high concentration complements factor H and attractin. The differences were considered significant at p < 0.05. It was found that the instability of atherosclerotic plaques is associated with the concentration of proteins: afamin, attractin, components of the complement system, hemopexin and haptoglobin. The data of our study showed the association of some blood proteins with the instability of atherosclerotic plaques in coronary atherosclerosis. Their potential role in the development of this disease and the possibility of using the studied proteins as biomarkers requires further research.

Adipokine Levels in Men with Coronary Atherosclerosis on the Background of Abdominal Obesity.

Background. Obesity is associated with dyslipidemia, and excess body fat is associated with unfavorable levels of adipokines and markers of inflammation. The goal of research. To study the level of adipokines and markers of inflammation, their associations with unstable atherosclerotic plaques in men with coronary atherosclerosis on the background of abdominal obesity. Materials and methods. The study involved 82 men aged 40-77 years with coronary atherosclerosis after endarterectomy from the coronary arteries. We divided all men into two groups: 37 men (45.1%) with unstable atherosclerotic plaques, and 45 men (54.9%) who had stable plaques. Obesity was established at a BMI of ≥30 kg/m2. The levels of adipokines and markers of inflammation in the blood were determined by multiplex analysis. Results. In patients with obesity and unstable plaques, the levels of C-peptide, TNFa and IL-6 were 1.8, 1.6, and 2.8 times higher, respectively, than in patients with obesity and stable plaques. The chance of having an unstable plaque increases with an increase in TNFa by 49% in obese patients and decreases with an increase in insulin by 3% in non-obese patients. Conclusions. In men with coronary atherosclerosis and obesity, unstable atherosclerotic plaques in the coronary arteries are directly associated with the level of TNF-α.

Blood Levels of Indicators of Lower Respiratory Tract Damage in Chronic Bronchitis in Patients with Abdominal Obesity.

OBJECTIVE: to study biomolecules associated with pathology in the respiratory system, in particular, with the development of chronic bronchitis in patients with abdominal obesity. MATERIALS AND METHODS: This is a pilot study. The main group consisted of 158 people with chronic bronchitis, divided into two subgroups: one with abdominal obesity, and the other without it. The control group consisted of 68 people without chronic bronchitis. We determined the blood levels of SP-A, SP-D, α1-antitrypsin, CC16, PARC, and RELM-ß. RESULTS: In the first subgroup, patients significantly more often complained of coughing, experienced shortness of breath 1.5 times more often with light physical exertion and 2.7 times more often with moderate physical exertion. In these patients, a Tiffeneau-Pinelli index (FEV1/FVC) below 70% was 1.8 times more common, more patients had FEV1 and FVC of less than 80%, and presented a statistically significant decrease in SP-A, α1-antitrypsin, CC16 levels and an increase in PARC levels than in the second subgroup. CONCLUSION: In patients with chronic bronchitis and abdominal obesity, there is a decrease in the levels of SP-A, α1-antitrypsin, CC16 and an increase in the level of PARC compared with patients without abdominal obesity, which is probably due to the presence of an additional source of chronic inflammation associated with adipose tissue.

Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population.

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.

Associations of Antioxidant Enzymes with the Concentration of Fatty Acids in the Blood of Men with Coronary Artery Atherosclerosis.

OBJECTIVE: To identify associations of fatty acids (FAs) with the antioxidant enzymes in the blood of men with coronary atherosclerosis and ischemic heart disease (IHD). METHODS: The study included 80 patients: control group-20 men without IHD, the core group-60 men with IHD. The core group was divided into subgroups: subgroup A-with the presence of vulnerable atherosclerotic plaques, subgroup B-with the absence of vulnerable atherosclerotic plaques. We analyzed the levels of FAs, free radicals, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the blood. RESULTS: Patients with IHD, compared with the control group: (1) had higher levels of SOD, CAT, myristic, palmitic, palmitoleic, and octadecenoic FAs; (2) had lower levels of GPx, α-linolenic, docosapentaenoic, docosahexaenoic, and arachidonic FAs. In subgroup A there were found: (1) negative associations of SOD-with linoleic, eicosatrienoic, arachidonic, eicosapentaenoic, docosapentaenoic and docosahexaenoic FAs, positive associations-with palmitic acid; (2) positive correlations of CAT level with palmitoleic and stearic acids; (3) negative associations between of GPx and palmitic, palmitoleic, stearic and octadecenoic FAs. CONCLUSIONS: Changes in the levels of antioxidant enzymes, and a disbalance of the FAs profile, probably indicate active oxidative processes in the body and may indicate the presence of atherosclerotic changes in the vessels.

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.

Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD.

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.

The Influence of Calcification Factors and Endothelial-Dysfunction Factors on the Development of Unstable Atherosclerotic Plaques.

BACKGROUND: This study aimed to evaluate changes in markers of calcification and of endothelial dysfunction during the development of calcification and instability of atherosclerotic plaques and to identify associations of calcification factors with the formation of unstable plaques. METHODS: We analyzed 44 male patients with coronary atherosclerosis who underwent endarterectomy in coronary arteries during coronary bypass surgery. The endarterectomy material (intima/media) was examined using histological and biochemical methods, and the stability and calcification degree of atherosclerotic plaques were assessed. In homogenates of the tissue samples and in blood, concentrations of osteoprotegerin, osteocalcin, osteopontin, osteonectin, monocyte-chemoattractant protein type 1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin were determined by enzyme immunoassays. RESULTS: Unstable atherosclerotic plaques proved to be calcified more frequently (80.4% of plaques) than stable ones (45.0%). Osteonectin, E-selectin, and sVCAM-1 levels were lower in unstable plaques and plaques with large calcification deposits. Osteocalcin content increased with the increasing size of the calcification deposits in plaque. Blood osteocalcin concentration directly correlated with osteocalcin concentration in atherosclerotic plaques and was higher in the blood of patients with calcified plaques in coronary arteries. CONCLUSIONS: The results provide the basis for further research on the suitability of osteocalcin as a potential biomarker of an unstable calcified atherosclerotic plaque in a coronary artery.

Changes in the proteomic profile of blood serum in coronary atherosclerosis.

BACKGROUND: Our aim was to study changes in the serum proteomic profile in coronary atherosclerosis. METHODS: The study involved two groups of patients: 1) men with coronary heart disease and coronary atherosclerosis (n = 15); 2) control (n = 15): men without coronary heart disease. The object of this study was blood serum. Separation of proteins for the investigation of differences in serum protein components was performed by two-dimensional electrophoresis. Identification of protein fractions was carried out using peptide mass maps by the matrix-assisted laser desorption ionization method. RESULTS: In blood serum samples from patients with coronary atherosclerosis, protein separation in two-dimensional gels with mass-spectrometric identification revealed an increase of some proteins: hemopexin, transthyretin (monomeric form), retinol-binding protein 4, and components of the complement system: C3 (chain B) and C9. There was a decrease of some proteins: kininogen, zinc finger protein 133, and B-cell CLL/lymphoma 6 member B protein. Comparisons between the experimental and control group were carried out in protein fractions where the protein amount differed more than 1.5-fold (p < 0.05). CONCLUSIONS: Proteome profiling of serum revealed a change in the content of kininogen, hemopexin, transthyretin, retinol-binding protein, and proteins of the complement system (C9, and C3) in coronary atherosclerosis. The contribution to the differential expression of a protein was often made by isoforms of the protein, particularly transthyretin. The change in the concentrations of functionally interacting proteins, such as transthyretin and retinol-binding protein, were noted.

The Short Overview on the Relevance of Fatty Acids for Human Cardiovascular Disorders.

This review presents existing evidence of the influence of saturated and unsaturated fatty acids on cardiovascular diseases (CVD). Data are discussed regarding the roles of the most relevant fatty acids, such as myristic (C14:0), palmitic (C16:0), stearic (C18:0), palmitoleic (C16:1), oleic (C18:1), linoleic (C18:2), α-linolenic (C18:3, ω-3), γ-linolenic (C18:3, ω-6), arachidonic (C20:4), eicosapentaenoic (C20:5), docosahexaenoic (C22:6), and docosapentaenoic (C22:5) acid. The accumulated knowledge has expanded the understanding of the involvement of fatty acids in metabolic processes, thereby enabling the transition from basic exploratory studies to practical issues of application of these biomolecules to CVD treatment. In the future, these findings are expected to facilitate the interpretation and prognosis of changes in metabolic lipid aberrations in CVD.

Changes in the blood fatty-acid profile associated with oxidative-antioxidant disturbances in coronary atherosclerosis.

BACKGROUND: The objective of this work was to study the profile of fatty acids and to search for associations of fatty acids with oxidative-antioxidant parameters and an oxidative-inflammatory biomarker (lipoprotein-associated phospholipase A2) in men with coronary atherosclerosis and coronary heart disease. METHODS: Analysis of 20 fatty acids was performed in 60 men with angiographically confirmed coronary atherosclerosis and coronary heart disease and in a control group of men without coronary heart disease. Serum fatty-acid content was evaluated by high-performance gas-liquid chromatography. The blood levels of oxidative stress, total antioxidative defence, and lipoprotein-associated phospholipase 2 were analyzed. RESULTS: In the group of men with coronary atherosclerosis the levels of myristic and palmitic fatty acids were higher by 59% and 22%, respectively. An increase in the weight percentage of monounsaturated fatty acids was noted, such as palmitoleic, oleic, and octadecenic. Significantly lower levels of polyunsaturated fatty acids, such as linolic, eicosadienoic, eicosatrienoic, arachidonic, eicosapentaenoic, glinolenic, docosapentaenoic, and docosahexaenoic were detected in the group with coronary atherosclerosis. The lipoprotein-associated phospholipase A2 level was higher by 48%. Oxidative stress was higher by 17%, and the total antioxidant defence in serum was lower by 45%. We found correlations between fatty acids and oxidative-antioxidative alterations. The relative risk of vulnerable atherosclerotic plaques correlated with increased levels of palmitic, stearic, oleic, and linolic fatty acids. CONCLUSIONS: Significant alterations in the profile of fatty acids are associated with oxidative-antioxidative alterations and are accompanied by an increase in free-radical formation, which can probably serve as a risk factor of atherosclerosis.

The Role of Secretory Activity Molecules of Visceral Adipocytes in Abdominal Obesity in the Development of Cardiovascular Disease: A Review.

Adipose tissue is considered one of the endocrine organs in the body because of its ability to synthesize and release a large number of hormones, cytokines, and growth and vasoactive factors that influence a variety of physiological and pathophysiological processes, such as vascular tone, inflammation, vascular smooth muscle cell migration, endothelial function, and vascular redox state. Moreover, genetic factors substantially contribute to the risk of obesity. Research into the biochemical effects of molecules secreted by visceral adipocytes as well as their molecular genetic characteristics is actively conducted around the world mostly in relation to pathologies of the cardiovascular system, metabolic syndrome, and diabetes mellitus. Adipokines could be developed into biomarkers for diagnosis, prognosis, and therapeutic targets in different diseases. This review describes the relevance of secretory activity molecules of visceral adipocytes in cardiovascular disease associated abdominal obesity.

A Proteomic Study of Atherosclerotic Plaques in Men with Coronary Atherosclerosis.

BACKGROUND: To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. METHODS: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. RESULTS: Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold (p < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin ß-chain, actin, keratin, tubulin ß-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic-dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. CONCLUSION: This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis.