Markers Of Endothelial Dysfunction Research Articles

Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5mg/kg BID, n = 5), Group C (CER-001 10mg/kg BID, n = 5), and Group D (CER-001 20mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Effects of Probiotics and Fibers on Markers of Nephropathy and Endothelial Dysfunction in Persons with Type 1 Diabetes and Albuminuria

Effects of Probiotics and Fibers on Markers of Nephropathy and Endothelial Dysfunction in Persons with Type 1 Diabetes and Albuminuria

Elevated indoleamine 2,3-dioxygenase activity is associated with endothelial dysfunction in people living with HIV and ROS production in human aortic endothelial cells in vitro.

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.

Изучение эффективности лечения эндотелиальной сосудистой дисфункции при различных стадиях первичной открытоугольной глаукомы

Relevance. According to literary sources, POAG is considered as a chain of interaction of etiological and pathogenetic factors, among which the leading role is played by genetic predisposition, general changes, ischemia, primary local functional and dystrophic changes, disturbances in hydrostatics and hydrodynamics of the eye, increased intraocular pressure, vascular disorders, dystrophy and tissue degeneration. Purpose of the study. To assess the severity of endothelial dysfunction in patients with different stages of primary open-angle glaucoma during complex therapy. Material and research methods. The study included 92 patients with POAG aged 65 to 80 years, who were divided into three groups. We studied the levels of endothelin-1, VEGF and von Willebrand factor before and after the recommended treatment in patients with POAG. Conclusion. The developed complex therapy of various stages in patients with POAG contributed to the correction of the identified disorders in relation to markers of endothelial dysfunction. The features of changes in ED markers in patients with POAG have been established; low levels of von Willebrand factor, VEGF and endothelin-1, which indicates the role of pathogenetic factors in the formation of endothelial dysfunction and the importance of studying markers of endothelial dysfunction. Keywords: primary open-angle glaucoma, endothelial markers, von Willebrand factor, VEGF, endothelin-1, complex therapy

Physical exercise in patients with testicular cancer treated with bleomycin, etoposide and cisplatin chemotherapy: pulmonary and vascular endothelial function—an exploratory analysis

PurposeBleomycin, etoposide, and cisplatin combination chemotherapy (BEP) improves the survival of patients with testicular cancer, but is associated with potentially life-threatening toxicities like pneumonitis and thromboembolic events. This study explored the effects of physical exercise in patients with testicular cancer during or after BEP-chemotherapy on pulmonary and vascular endothelial toxicity.MethodsIn this post hoc analysis of a multicenter randomized clinical trial (NCT01642680), patients with metastatic testicular cancer scheduled to receive BEP-chemotherapy were randomized to a 24-week exercise intervention, initiated during (group A) or after BEP-chemotherapy (group B). Endpoints were pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), lung transfer-coefficient and transfer factor for carbon monoxide (KCO, DLCO) and markers of vascular endothelial dysfunction (von Willebrand factor (vWF) and factor VIII).ResultsThirty patients were included. Post-chemotherapy, patients declined less in FVC, FEV1 and DLCO in group A compared to group B. Post-chemotherapy, vWF and factor VIII were significantly lower in group A compared to group B. After completion of exercise, started either during BEP-chemotherapy or thereafter, no between-group differences were found. At 1-year post-intervention, significant between-group differences were found in favour of group A in DLCO and KCO.ConclusionsPatients who exercised during BEP-chemotherapy better preserved FVC, FEV1 and DLCO, measured directly post-chemotherapy and 1-year post-intervention (DLCO, KCO). This coincided with less increase in vWF and factor VIII measured directly post-chemotherapy. These data support a beneficial role of a physical exercise intervention during BEP-chemotherapy on pulmonary and vascular damage in patients with testicular cancer.Trial registryOptimal Timing of Physical Activity in Cancer Treatment (ACT) Registry URL: https://clinicaltrials.gov/ct2/show/NCT01642680. Trial registration number: NCT01642680.

Endothelial dysfunction in patients with obesity and type 2 diabetes mellitus or normoglycemia: assessment of specific markers

BACKGROUND: One of the function of the endothelium is the maintenance of body's homeostasis. Endothelial dysfunction is known to be profoundly implicated in the pathogenesis of cardiovascular diseases (CVD). The presence of diabetes mellitus significantly increases the risks of CVD. Type 2 diabetes mellitus (T2DM) is often observed in obesity, however, there is a population of people with obesity, who do not develop T2DM for a long time.AIM: To compare the level of markers of endothelial dysfunction in two groups of individuals (without T2DM and with T2DM), as well as to evaluate the impact of cardioprotective medication (GPP-1 and SGLT-2) on these markers.MATERIALS AND METHODS: We recruited 2 groups of patients with obesity into this study: the 1st group with no carbohydrate metabolism disorders, the 2nd with T2DM. Several markers of endothelial dysfunction were evaluated: human von Willebrand factor (VWF), vascular endothelial growth factor A (VEGF-A), soluble form E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM1).RESULTS: A significant increase in sE-Selectin was seen in the group of patients with obesity and T2DM compared with those without carbohydrate metabolism disorders (46.65 [36.23; 66.66] vs 33.05 [22.1;53.31] ng/ml). There were no differences in the level of markers of endothelial dysfunction in the subgroups of patients with T2DM with HbA1c &lt; 8% and &gt;8%. There was also no effect of cardioprotective drugs (SGLT-2 and / or GPP-1) on any of endothelial dysfunction markers in individuals with T2DM.CONCLUSION: We suggest that an increase in sE-selectin may be an early marker of endothelial dysfunction in obese individuals and T2DM.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, isbelieved to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. None of the patients had known underlying cardiovascular disease. The mean age was 13.18±2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42±0.06 vs. healthy controls: 0.34±0.04mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97±10.32 vs. 77.56±8.50 %, (OI group: 7.00±3.06 vs. healthy controls: 12.14±1.99, p=0.56), and fractional shortening was 42.68±11.94 vs. 40.23±7.99 %, (p=0.35), in OI patients and controls, respectively. Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

Metabolic syndrome, soluble CD40L, and biomarkers of endothelial dysfunction in people living with HIV.

In the present study, we aimed to investigate the association between soluble CD40 ligand (sCD40L, a marker of platelet activation), soluble thrombomodulin, and syndecan-1 (both well-described markers of endothelial dysfunction) and metabolic syndrome in a large cohort of well-treated people with HIV (PWH) and to elucidate their association with HIV-specific variables. We included 862 PWH with undetectable viral replication. Our hypotheses were tested using uni- and multivariable logistic regression models a priori adjusted for well-known confounders. While no association of soluble thrombomodulin and syndecan-1 with MetS was found, high levels of sCD40L (aOR 1.54 [1.07-2.22]) were associated with excess risk of MetS. Given the previously described association between sCD40L, vascular inflammation and endothelial damage, the results presented in our study may suggest a potential role for sCD40L in the well-known association between cardiometabolic comorbidity and HIV infection.

Blebbing of the plasma membrane of lymphocytes as a marker of endothelial dysfunction in the development of post-resection insufficiency in patients with focal liver lesions

Purpose of the study. To evaluate the intensity of blebbing of the plasma membrane of lymphocytes and the formation of microparticles of lymphocytic origin in patients with postresection hepatic failure. Material and methods. The study involved 54 patients with focal liver diseases. The study involved 32 (59%) women, 22 (41%) men. The average age was 59.5 [49.75; 66,00]. Patients were divided into groups, 1 group - 10 patients with developed acute liver failure and 2 group - 44 patients with a favorable course of postoperative period. The following surgical interventions were performed: 36 (67%) patients underwent surgery - laparotomy, segmental liver resection, 10 (18%) - left-sided hemihepatectomy and 8 (15%) - right-sided hemihepatectomy. Results. Predictors of early postoperative hepatic failure are a decrease in initial blebbing and an increase in terminal blebbing and free microparticles of lymphocytic origin. Conclusions. Thus, changes in lymphocyte blebbing and the presence of free microparticles of lymphocytic origin are due to the development of endothelial insufficiency and apoptosis of lymphocytes in the context of liver failure and are determined by the reduced function of residual liver volume.

Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.

Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19. Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes. In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies. This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).

SAT042 Impact Of Aerobic Exercise On The Circulating Endothelial Progenitor Cells And Inflammation Markers In Type 1 Diabetes

Abstract Disclosure: C.K. Maraschin: None. P.M. Bock: None. R.B. Monteiro: None. A. Alegretti: None. P.L. Lopes: None. L.P. Santos: None. L. Helal: None. R. Moraes: None. D.U. de Moraes: None. B.D. Schaan: None. The circulating levels of endothelial progenitor cells (EPCs) is a marker of endothelial dysfunction in many chronic diseases, including diabetes mellitus. Increasing the amount of circulating EPCs through exercise may be a viable strategy for improving endothelial function. However, differences in EPC levels between individuals with and without diabetes and the responses of EPCs to exercise sessions were not previously studied. We sought to determine the number of circulating EPCs by flow cytometry in subjects with or without type 1 diabetes (T1DM), and to elucidate the independent or combined responses of EPC populations and inflammatory markers in response to one bout of intense aerobic exercise. This was a non-randomized controlled trial. Fifteen adult males, ages 18–65, with T1DM were included. Patients with high glycemia in the morning of the study or with chronic diabetic complications that made it difficult to perform the protocol were excluded. Fifteen healthy, non-obese, non-smoking individuals were recruited as controls. All included subjects underwent an aerobic exercise session on a cycle ergometer for 30 minutes at 60% of the predetermined peak heart rate. Blood samples were collected to evaluate plasma glucose levels, glycated hemoglobin (HbA1c), total and HDL cholesterol, tumor necrosis factor alpha (TNFa), interleukin 6 (IL-6), and EPCs (CD45dim/CD34+/KDR+) before and after the exercise session. Individuals with T1DM presented higher fasting plasma glucose (197.3 ± 90.0 mg/dL vs. 88 ± 11.2 mg/dL, p &amp;lt; 0.01) and HbA1c levels (7.9 ± 1.5 vs. 5.0 ± 0.3%, p &amp;lt; 0.01), while peak VO2 was higher in controls (37.6 ± 8.4 vs. 29.1 ± 10.9 mL.kg-1.min-1, p = 0.03). A complete blood count analysis showed increases in white blood cells [0.8 (0.1, 1.4) and 1.0 (0.4, 1.6) x103/µL, p &amp;lt; 0.001] and neutrophils [0.9 (0.3, 1.4) and 0.9 (0.3, 1.4) x103/µL, p &amp;lt; 0.001] in both groups after exercise. There was no difference within and between groups for EPCs before and after the aerobic exercise session - delta 0.02 (-0.04, 0.08) among controls and 0.00 (-0.01, 0.01) among individuals with T1DM]. No difference was observed in the levels of TNF-α among controls [210.2 (142.1 - 401.2); 191.3 (136.4 - 350.5) pg/mL] and individuals with T1DM [463.8 (201.4 - 4306.0); 482.7 (143.8 – 4304.3) pg/mL], before and 60 minutes after the exercise session, respectively. The IL-6 did not show any difference in controls [148.2 (147.5 – 148.6); 148.2 (147.7 – 148.6) pg/mL] and in those with T1DM [147.2 (145.9 – 147.7); 147.2 (146.8 – 147.8) pg/mL], before and 60 minutes after exercise, respectively. Patients with T1DM and healthy controls did not show a different response on EPCs levels after an acute session of aerobic exercise, most likely because they do not have a chronic inflammatory state. Hence, our study suggests that aerobic exercise (peak of 60% VO2) has the same effect on endothelial function in patients with or without T1DM. Presentation: Saturday, June 17, 2023

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion.

Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.

Flow-mediated dilation as a marker of endothelial dysfunction in pulmonary diseases: A narrative review

The endothelium is an active and crucial component of vessels and produces several key regulatory factors for the homeostasis of the entire organism. Endothelial function can be investigated invasively or non-invasively, both in the coronary and peripheral circulation. A widely accepted method for the assessment of endothelial function is measurement of flow-mediated dilation (FMD), which evaluates the vascular response to changes in blood flow.In this current review, we describe FMD applications in the clinical setting of different respiratory diseases: acute SARS-COV2 infection, pulmonary embolism; post-acute SARS-COV2 infection, Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apneas Syndrome, Pulmonary Hypertension, Interstitial Lung Diseases.Emerging evidence shows that FMD might be an effective tool to assess the cardiovascular risk in patients suffering from the undermentioned respiratory diseases as well as an independent predictive factor of disease severity and/or recovery.

Study of the state of th vascular endothelium in various forms of coronary heart disease

Purpose of the study: to investigate changes in markers of endothelial dysfunction and hemostasis system in patients with different forms of CHD on the background of treatment and before it.Materials and methods of the study. In order to fulfill the set tasks, 60 patients with different forms of CHD: stenocardia and myocardial infarction (according to the classification of the Canadian Association of Cardiology (L. Cam-peau, 1976)), 60 patients with different forms of CHD were examined during the study. Campeau, 1976), VNOC (2004), recommendations of the European Society of Cardiology (2007)), aged from 50 to 75 years (mean age 62.6 ± 3.5 and 65.1 ± 3.6 years, respectively) and 20 practically healthy individuals (without signs of CHD), comparable in age (mean age 62.7 ± 3.7 years), who constituted the control group. For comparative analysis of the results before and after treatment the subjects were divided into three groups: Group I - control group, respondents without CHD; Group II - patients with stable angina II and III functional classes (FC); Group III - patients with postinfarction cardiosclerosis, i.e. those who had undergone Ml.Results and their discussion Several risk factors were identified in the majority of hospitalized patients. CHD of II and III FC was more often registered in women (60%); men who had undergone myocardial infarction accounted for 63.3%, the indices were statistically insignificant (p &gt;0.05). The main cardiovascular risk factors (obesity, arterial hypertension, body mass index and total cholesterol) were significantly higher (in % ratio) in patients of groups ll-lll compared to group I (p&lt;0.001), but the cholesterol content and body mass index were on average higher in group II (4.5 ± 1.0 and 33.0 ± 1.3, respectively) than in group III (4.2 ±1.1 and 30.6 ± 2.6, respectively). As for the duration of the disease, group III patients were characterized by a longer history and a higher frequency of heart failure, i.e. patients in this group had a more severe clinical status (p &gt; 0.05). It should be noted that of the total number of patients (n = 80), rural residents accounted for 46.25% and city dwellers for 53.75%.ConclusionsThe presence of a higher degree of endothelial dysfunction is observed in patients who underwent myocardial infarction, in contrast to the stable form of angina pectoris without myocardial infarction in the anamnesis. The progression and deterioration of vascular endothelium is mostly associated with the presence of hyperhomocysteinemia, and the most pronounced changes in endothelial function are determined in patients with a combination of cardiovascular risk factors. In different forms of CHD the increased content of DEK and homocysteine in blood serum, increasing in parallel with the severity of clinical course, their level correlates with the degree of endothelial dysfunction. A direct correlation between hemostasis markers (von-Willebrand factor, fibrinogen and platelets) and DEK was revealed. The greatest changes in vascular-thrombocytic and coagulation hemostasis are observed in patients with IMI than in patients with stenocardia.

ФЕНОТИП ВИБРАЦИОННОЙ БОЛЕЗНИ В СОЧЕТАНИИ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ: НОВЫЕ МИШЕНИ НУТРИТИВНО-МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ

Introduction. Comorbidity in the modern world is a predictor of a more severe course of most diseases and has a significant impact on the characteristics, course and outcomes of the disease in the structure of occupational pathology. This is characterized by an increase in clinical syndromes, a deterioration in the quality of life and disability. Purpose of the study. Optimization of diagnostics in the form of studying clinical, functional and nutritional and metabolic parameters in professional patients on a model of comorbid pathology of vibration disease in combination with arterial hypertension. Materials and methods. In the course of a single-stage open, descriptive, comparative clinical study, 431 patients were examined in the conditions of the regional center of professional pathology in the city of Novosibirsk. Patients were divided into groups: patients with isolated vibration disease (n = 104), a group of comorbid WB+AH model (n = 101), a comparison group were patients with arterial hypertension (107 patients), a control group of conditionally healthy individuals (119 people) . The study duration was 4.9 ± 0.25 years. The indicators of the main analyzers, nutritional and metabolic status, nutritional adequacy, indicators of protein, lipid, carbohydrate metabolism, adipokine status, blood 25OH vitamin D, indicators of endothelial dysfunction, RAAS components, oxidative stress and systemic inflammation were evaluated. Results and its discussion. With VP+AH, the most unfavorable metabolic status was revealed. In this group, higher levels of insulin, glycated hemoglobin, HOMA-IR index, total cholesterol, LDL, triglycerides, atherogenic coefficient were determined in comparison with the isolated WB group and the control group, respectively. The phenotype of WB and AH shows the highest concentration of resistin, significantly higher than in the comparison and control groups, against the background of low levels of adiponectin, as well as an increase in the level of free leptin against the background of a decrease in the leptin-binding receptor. In the course of bioimpedancemetry, significant deviations were found in the group of the comorbid model of HF in combination with AH in the following indicators: an increase in fat mass normalized for growth and extracellular fluid with a decrease in the parameters of lean and active cell mass and phase angle. In the group of the comorbid model of WB and AH, changes were also detected in the following indicators of the molecular endotype: an increase in markers of oxidative stress (total antioxidant status of serum, Cu/ZnSOD, concentration of free radicals, lipid peroxides, protein oxidation products), the RAAS system, markers of endothelial dysfunction (endothelin 1, nitric oxide, tissue factor) and systemic inflammation (IL1 β, MCP-1, FGF 2, cardiotrophin, MMP 1, MMP 9, pentraxin 3, neutrophil elastase). Conclusions. A variant of the comorbid model is characterized by clinical-molecular and nutritional-metabolic features in professional patients, which are caused by a multifactorial pathomorphosis of a combination of vibration disease and arterial hypertension. In this variant, indicators of worse metabolic and adipokine status relative to the compared groups, pronounced processes of systemic inflammation, oxidative stress, and endothelial dysfunction were revealed.

Serum Endocan Levels in Postmenopausal Women with Metabolic Syndrome.

Aim: Studies that explored endocan (as a novel marker of endothelial dysfunction) in relation to metabolic syndrome (MetS) are scarce and show discordant results. Importantly, no study has yet examined serum endocan levels in exclusively postmenopausal women with MetS and free of diabetes. Oxidative stress and inflammation are the key features of MetS and consequently cardiovascular diseases. Hence, we aimed to explore the potential relationship between endocan, oxidative stress [i.e., determined by total antioxidant status, total oxidant status, and pro-oxidant/antioxidant balance (PAB)], inflammation, and MetS in a cohort of postmenopausal women. Methods: A total of 126 postmenopausal women were included consecutively. MetS was diagnosed following the International Diabetes Federation criteria. Results: Higher serum endocan levels were found in MetS group as compared with MetS-free counterparts [6.03 (3.47-10.37) pg/mL vs. 2.27 (1.49-3.50) pg/mL, P < 0.001]. Endocan showed good discriminatory ability toward MetS [area under the curve (AUC) = 0.809]. Besides age, the inclusion of oxidative stress and inflammation biomarkers, such as PAB and high-sensitivity C-reactive protein (hsCRP), the AUC for discrimination postmenopausal women with MetS from MetS-free women was 0.845. Conclusion: Postmenopausal women with MetS exhibited almost 2.7 times higher serum endocan level as compared with MetS-free middle-aged women. Endocan showed good discriminatory ability toward MetS and could be a diagnostic marker in MetS. Similar results were confirmed when added an age, oxidative stress, and inflammation biomarkers (i.e., PAB and hsCRP) were included for the discrimination of postmenopausal with MetS from MetS-free women.

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy

RationaleThe global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy. ObjectiveThe redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis. MethodsFor this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed. ResultsFor all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium. ConclusionDapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

OP08_4. Progesterone reduces inflammation, markers of endothelial dysfunction and maternal blood pressure in response to preeclampsia

OP08_4. Progesterone reduces inflammation, markers of endothelial dysfunction and maternal blood pressure in response to preeclampsia

Renal hemodynamics in patients with resistant hypertension and type 2 diabetes mellitus.

Aim To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p&lt;0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p&lt;0.001), increases in concentrations of hsCRP (r=0.35, p&lt;0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p&lt;0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p&lt;0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR &lt;60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).