Highlights The molecular profile of dysfunctional endothelium in coronary artery disease is characterized by increased concentrations of the endothelial glycocalyx components SDC1 and ESM1, pro-inflammatory cell adhesion molecules ICAM1, VCAM1, and E-selectin, VEGFR2, and vWF, and decreased concentrations of SDC2, ENG, and ET-1 compared with apparently healthy individuals. Age-associated changes in the molecular profile are predominantly observed in individuals with normal endothelial function, whereas in coronary artery disease, most of the studied markers show no association with age, suggesting a predominant influence of endothelial dysfunction on their concentrations. In coronary artery disease, the relationships between endothelial glycocalyx components, markers of pro-inflammatory activation, and angiogenic regulation are altered, indicating changes not only in the concentrations of individual markers but also in the relationships among molecular markers of dysfunctional endothelium. Aim. To characterize age-associated changes in the molecular profile of endothelial dysfunction in patients with coronary heart disease (CHD) and apparently healthy individuals based on a comparative analysis of molecular marker concentrations, their interrelationships, and associations with age. Methods. The study included 31 apparently healthy volunteers (mean age, 34 years) and 106 patients with CAD (mean age, 64.5 years) who underwent on-pump coronary artery bypass graft surgery. The concentrations of the endothelial glycocalyx components SDC1, SDC2, SDC4, and ESM1; cell adhesion molecules ICAM1, VCAM1, and E-selectin; constitutive endothelial cell receptor markers VEGFR2 and ENG; as well as vWF and ET-1 were measured by enzyme-linked immunosorbent assay. The concentrations of the studied markers were compared between the groups, and correlation analysis was performed to assess their associations with age and relationships with each other. Results. Patients with CAD had higher concentrations of SDC1, ESM1, ICAM1, VCAM1, E-selectin, VEGFR2, and vWF and lower concentrations of SDC2, ENG, and ET-1 compared with apparently healthy individuals, whereas SDC4 concentrations did not differ between the groups. In the overall sample, age positively correlated with ICAM1 (r = 0.4573), SDC1 (r = 0.3530), and ESM1 (r = 0.3781) concentrations and negatively correlated with ET-1 (r = −0.5588). However, none of the markers showed an association with age that was consistently observed in both groups and in the overall sample. Among apparently healthy individuals, age correlated with VCAM1 (r = 0.4122) and vWF (r = −0.5420), whereas most age-related associations were absent in patients with CAD. Analysis of relationships between the markers demonstrated correlations between glycocalyx components, molecules involved in pro-inflammatory activation, and markers of angiogenic regulation in both groups; however, the strength and pattern of individual relationships differed depending on the functional state of the endothelium. Conclusion. CAD is associated with a distinct endothelial molecular profile characterized by alterations in glycocalyx components, pro-inflammatory activation, angiogenic regulation, and hemostasis. Age-associated changes in the studied markers are predominantly observed in individuals with normal endothelial function, whereas most age-related associations are absent in CAD. These findings suggest that endothelial dysfunction becomes a dominant factor determining the endothelial molecular profile in CAD, thereby reducing the independent contribution of age.
Highlights An increasing amount of data confirms the link between inflammatory markers and electrophysiological changes in the myocardium. QTc interval prolongation is associated with female gender, blood pressure levels, plasma glucose levels, and ischemic heart disease in residents of Novosibirsk. QTc interval prolongation is associated with elevated fibrinogen levels, independent of other cardiometabolic risk factors and ischemic heart disease in residents of Novosibirsk. Aim. To study the association of the QT interval with fibrinogen along with cardiometabolic risk factors and coronary heart disease in a sample of Novosibirsk residents. Methods. The study was conducted as part of the ESSE-RF3 study on the basis of the IIPM – branch of the IC&G SB RAS. The study included 1,042 residents of Novosibirsk (510 (48.9%) men) aged 35–74 years. The examination program included blood sampling, demographic and social data collection, anthropometry, blood pressure (BP) measurement, and electrocardiogram (ECG) recording. The threshold value of fibrinogen was considered to be ≥ 4 g/L. The presence of coronary heart disease (CHD) and its categories were determined based on the Rose G.A. questionnaire and an ECG assessment according to the Minnesota Code. The QT interval was measured in lead V5. A value of more than 75 percentile was chosen as the QT prolongation (409 ms, n = 261 (25%)). Results. QT prolongation was more common in women (155/532 (29.1%) vs. 106/510 (20.8%), p = 0.002), in patients with high blood pressure (185/624 (29.6%) vs. 76/418 (18.2%), p < 0.001), and high glucose levels (105/307 (34.2%) vs. 156/735 (21.2%), p < 0.001), fibrinogen levels of more than 4 g/L (37/78 (47.4%) vs. 224/964 (23.2%), p < 0.001), the presence of coronary heart disease (62/162 (38.3%) vs. 18/41 (43.9%) vs. 181/839 (21.6%), p < 0.001). According to logistic regression analysis, prolongation of the QT interval is associated with female gender (OR 1.846, 95% CI 1.336–2.551, p < 0.001), blood pressure ≥ 140/90 mmHg (OR 1.454, 95% CI 1.054–2.005, p = 0.022), fasting plasma glucose ≥ 6.1 mmol/L (OR 1.603, 95%CI 1.145–2.245, p = 0.006), fibrinogen levels ≥ 4 g/L (OR 2.504, 95% CI 1.528–4.104, p < 0.001) and CHD (OR 1.336, 95% CI 1.106–1.613, p = 0.003), and the association with fibrinogen was the highest. Conclusion. Prolongation of the QTc interval is associated with fibrinogen levels independently of other cardiometabolic risk factors and coronary heart disease associated with QTc prolongation in Novosibirsk residents.
Highlights By 12 months of age, compared with 3 months, ApoE −/− mice exhibit increased expression of the pro-inflammatory cell adhesion molecules VCAM1/CD106, ICAM1/CD54, and SELE/CD62E in the aortic endothelium compared with the perivascular endothelium, particularly in female mice. By 12 months of age, compared with 3 months, ApoE −/− mice also demonstrate increased expression of the inflammasome-associated cytosolic protein NLRP3 and endothelial-to-mesenchymal transition in aortic endothelium as compared to perivascular endothelium. By 12 months of age, compared with 3 months, male ApoE −/− mice show increased expression of laminin, perlecan, and fibronectin, whilst female mice demonstrate elevated expression of laminin, nidogen-1, and type IV collagen in the basement membrane of the aortic intima compared with the aortic microvessels. Aim. To investigate age-dependent expression of endothelial activation markers in the aortic and perivascular endothelium in male and female hyperlipidemic mice. Methods. Cryosections of the aorta from male and female ApoE −/− mice aged 3, 9, and 12 months (n = 6 per time point) were stained with antibodies to pro-inflammatory cell adhesion molecules (VCAM1/CD106, ICAM1/CD54, SELE/CD62E), pro-inflammatory transcription factor NF-κB, inflammasome-associated cytosolic protein NLRP3, endothelial-to-mesenchymal transition transcription factors (Snail, Slug, TWIST1, and ZEB1), endothelial phenotype receptor markers (PECAM1/CD31, KDR/CD309, CDH5/CD144, MCAM/CD146, ENG/CD105, BSG/CD147, Tie2/CD202b, EFNB2, EPHB4), endothelial basement membrane components (laminin, perlecan, fibronectin, type IV collagen, nidogen-1, and nidogen-2), endothelial glycocalyx components (endocan, syndecan-1, syndecan-2, syndecan-4, thrombomodulin, and thrombospondin-1), mechanosensitive transcription factors (KLF2, KLF4, NRF2), and complement regulatory proteins (MAC-IP/CD59, DAF/CD55, MCP/CD46), followed by digital slide acquisition. Semi-quantitative analysis of protein expression in the endothelium was performed using ImageJ software. Results. By 12 months of age, compared with 3 months, ApoE −/− mice demonstrated increased expression of: 1) pro-inflammatory cell adhesion molecules VCAM1/CD106, ICAM1/CD54, and SELE/CD62E (in female mice) and ICAM1/CD54 (in male mice); 2) inflammasome-associated cytosolic protein NLRP3 (in female mice); 3) endothelial-to-mesenchymal transition transcription factors (both male and female mice); 4) endothelial phenotype receptor markers PECAM1/CD31, KDR/CD309, and EPHB4 (in female mice); 5) basement membrane components (laminin, perlecan, and fibronectin in male mice; laminin, nidogen-1, and type IV collagen in female mice) in the aortic endothelium compared with perivascular endothelium. No age-related trends were observed in the expression of endothelial glycocalyx components, mechanosensitive transcription factors, or complement regulatory proteins in both aortic and perivascular endothelium. Conclusion. By 12 months of age, aortic endothelium demonstrated a tendency toward pro-inflammatory activation compared with perivascular endothelium. Increased expression of basement membrane components may contribute to the binding of atherogenic lipoproteins and their retention in the intima.
Highlights The study provides the first extended in vitro assessment of UniLine bioprostheses across six standardized pressure modes: from hypotension to very severe hypertension, establishing reference hydrodynamic values for domestic heart valve technologies. The bioprostheses demonstrated high stability of essential performance metrics (effective orifice area 1.45–1.53 cm²; mean gradient 4.23–4.38 mmHg) under increasing hemodynamic loads, confirming the adequacy of their structural design and reliability across a broad spectrum of simulated clinical conditions. Regurgitation values under extreme loading revealed intrinsic variability of biological tissues, highlighting the need to account for biomechanical heterogeneity in future engineering optimization and comparative evaluation of domestic bioprosthetic Aim. To evaluate the hydrodynamic performance of the domestic atrioventricular bioprosthesis UniLine (size 26 mm) under multiple loading modes defined by GOST 31618.1-2012. Methods. Twelve prostheses were tested in vitro using the Pulse Duplicator II across six pressure modes: from hypotensive (60/40 mmHg) to very severe hypertension (210/120 mmHg). Heart rate was set at 70 bpm with 35% systolic duration. Three metrics were assessed: mean transvalvular gradient, effective orifice area, and regurgitant volume. Data are presented as median [25 th ; 75 th percentile]. Results . Effective orifice area remained stable across modes (1.45–1.53 cm²; range 1.39–1.81 cm²). Mean gradient remained low, from 4.23 mmHg in hypotension to 4.32–4.38 mmHg in severe/very severe hypertension (overall range 1.55–6.03 mmHg). Regurgitant volume increased with pressure load, from 2.66 to 4.09 mL/cycle (maximum 8.04 mL/cycle in individual tests). All parameters met GOST and ISO requirements. Conclusion . UniLine bioprostheses demonstrate stable hydrodynamic behavior across a broad range of loading conditions, characterized by low gradients, consistent effective orifice area, and acceptable regurgitation. These results provide reference values supporting further optimization and extended preclinical evaluation.
Hightlights The theoretical novelty of this study lies in expanding of current knowledge regarding the impact of public-private partnerships on the organization of outpatient renal replacement therapy for patients with chronic kidney disease within the compulsory health insurance system. Aim . To identify the main challenges in organizing renal replacement therapy in outpatient settings, including through the implementation of public-private partnerships in the compulsory health insurance system. Methods . The volumes of outpatient dialysis services in the nephrology specialty and their funding for the period 2016–2025 were assessed using data from the information system of the Tomsk Region Territorial Compulsory Health Insurance Fund. Planned and actual indicators for medical organizations were obtained by multiplying the dialysis service tariff by the approved volumes of services provided, as specified in the first and last decisions of the Commission for the Development of the Territorial Compulsory Health Insurance Program for each year of the study period. The volumes of medical services actually provided by Nephroline-Tomsk LLC and their funding were obtained from medical invoice registers. Results . Significant changes in the provision of outpatient renal replacement therapy in the Tomsk Region were identified during the study period. First, the number and organizational and legal structure of medical organizations providing these medical services have changed. Until 2016, dialysis services were provided by two state medical organizations; by 2025, the number of organizations increased to six, four of which were private. With an increase in the total volume of dialysis services by 1.5 times (2016 – 42,192 services, 2025 – 63,516 services), a decrease in outpatient renal replacement therapy in state medical organizations by 74% was revealed (a total of 18,307 and 4,726 services in 2016 and 2025, respectively). Funding for outpatient dialysis services for 2016–2025 increased by 2.2 times (204.17 and 456.84 million rubles in 2016 and 2025, respectively). This is due to an increase and redistribution of funding toward private medical organizations (2016 – 115.76 million rubles; 2025 – 420.85 million rubles). Volumes were distributed unevenly among private organizations, with Nephroline-Tomsk LLC usually having the highest number of dialysis cases. This organization has the longest and most continuous history of providing renal replacement therapy in the region, providing these services not only in the regional center but also in three districts, thereby increasing access to medical care. Conclusion . An increase in the share of outpatient renal replacement therapy volumes and funding for private medical organizations has been noted, while public (regional and federal) organizations focus on inpatient dialysis services. The issue of providing dialysis services can be resolved through broader integration of public-private partnerships into the healthcare system. Harmonization of terminology will improve the accuracy of planned volumes and funding for medical services.
