Markers Of Endothelial Dysfunction Research Articles

Effects of long-term almond consumption on markers for vascular function and cardiometabolic risk in men and women with prediabetes: results of a randomized, controlled cross-over trial.

The aim of this study was to investigate the long-term effects of almond consumption on peripheral vascular function, ambulant blood pressure profiles (ABP), and serum/plasma markers reflecting endothelial dysfunction and inflammation in participants with overweight/obesity and prediabetes. Thirty-four participants completed this single-blinded, randomized, cross-over trial with 5-month intervention and control periods, separated by a 2-month wash-out. During the intervention period, participants consumed 50g of whole almonds daily. At the end of each intervention period, peripheral vascular function was assessed by measuring the carotid-to-femoral and carotid-to-radial pulse wave velocities (PWVc-f and PWVc-r, respectively) and retinal microvascular calibers. Serum/plasma concentrations of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFα), serum amyloid A protein (SAA) and high-sensitivity C-reactive protein (hs-CRP) and 24-hour ABP were also analyzed. Almond consumption did not significantly affect arterial stiffness (PWVc-f and PWVc-r), while central retinal venular equivalent (CRVE) was minimally increased by 2μm (P = 0.019). Central retinal arteriolar equivalent (CRAE), the arteriolar-to-venular ratio (AVR), and endothelial and inflammatory serum/plasma markers showed no significant changes after almond consumption. Almond consumption reduced systolic blood pressure (SBP; -3 mmHg 24-hour P = 0.035, -4 mmHg daytime P = 0.046, and - 4 mmHg during nighttime P = 0.029), SBP variability during 24-hour, daytime, and nighttime (P = 0.005, P = 0.019, and P = 0.003, respectively), and diastolic blood pressure variability during nighttime (P ≤ 0.001). Almond consumption did not affect arterial stiffness, retinal microvasculature calibers, or serum and plasma markers for endothelial dysfunction and inflammation in participants with prediabetics, while BP and BP variability were improved. This clinical trial was registered in February 2018 as NCT03419702.

Visfatin and VEGF levels are not increased in adolescent girls with polycystic ovary syndrome

IntroductionPCOS is one of the most commonly occurring endocrinopathies among women and increasingly affects adolescent populations. The connection between PCOS and various endocrinological, psychological, and CVD is increasingly recognized. Some studies have shown elevated levels of visfatin and VEGF among patients with PCOS, which are markers of vascular endothelial dysfunction. In our study, we evaluated the concentration of these parameters, focusing solely on a group of adolescents with PCOS, to assess whether these early markers of CVD are present at an early stage of diagnosis.Material and methodsIn total, 80 adolescent girls participated in the study. 47 adolescents diagnosed with PCOS were included in the study group (mean age 15.68 ± 1.18 years, BMI 26.66 ± 6.41 kg/m2), while the remaining 33 regularly menstruating individuals (mean age 15.79 ± 1.22 years, BMI 25.44 ± 7.24 kg/m2) were assigned to the control group. Each participant underwent imaging, biochemical, and hormonal tests. Additionally, markers of endothelial dysfunction: VEGF and visfatin, were measured in all adolescents.ResultsBoth VEGF and visfatin levels did not differ significantly between PCOS and control group (p=0.30 and p=0.15, respectively). In the group of adolescent girls with PCOS, visfatin was significantly correlated with HDL, FSH, cortisol, and testosterone levels >55 ng/dl. VEGF was significantly correlated with fasting glucose, glucose levels after OGTT, estradiol, and waist circumference >80 cm.ConclusionIt can be indirectly inferred that both visfatin and VEGF should not be used as early markers for cardiometabolic complications among adolescent patients with PCOS. On the other hand, low visfatin levels, through their negative correlation with HDL, may have a protective effect on cardiovascular complications, while low VEGF levels, through their positive correlation with glucose levels, may have a protective influence on carbohydrate metabolism disorders.

Retinal Microvascular Changes in Association with Endothelial Glycocalyx Damage and Arterial Stiffness in Patients with Retinal Vein Occlusion: A Cross-Sectional Study

Background/Objectives: To investigate the potential association between the endothelial dysfunction and arterial stiffness with retinal changes observed through optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with retinal vein occlusion (RVO). Methods: Participants in this cross-sectional study were 28 patients with RVO. The demographic and clinical characteristics of all participants were recorded. Comprehensive ophthalmologic examinations were performed, including fundus photography, OCT and OCT-A. Endothelial dysfunction was assessed by measuring the endothelial glycocalyx thickness via the perfused boundary region (PBR5-25). Arterial stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (PWV), the central systolic and diastolic blood pressures (cSBP and cDBP) and the augmentation index (Aix). For each ophthalmological outcome, we generated a saturated linear regression model with demographic and systemic vascular parameters serving as independent variables. Regression coefficients with the corresponding 95% confidence intervals (CIs) were reported. A p value < 0.05 was considered as statistically significant. Results: A 1 m/s increase in PWV was associated with a 0.6% reduction in inferior macular vessel density (VD) (p = 0.050). A 10 mmHg increase in cSBP was associated with a 0.03 mm2 increase in foveal avascular zone (FAZ) area (p = 0.033). A 1% increase in Aix was associated with a 0.005 mm2 increase in FAZ area (p = 0.008). A 1 μm increase in PBR5-25 was associated, on average, with a 4.4% decrease in superior peripapillary VD (p = 0.027). Conclusions: In patients with RVO, structural and microvascular retinal parameters were significantly associated with markers of endothelial dysfunction and arterial stiffness.

Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension

Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. MethodsWe prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve PAH patients (n=22) and those who had a clinical indication to intensify therapy (n=19). In addition, we recruited 12 healthy people and clinically stable PAH patients (n=45) as controls who had two blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had NT-pro-BNP, 6-minute-walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. ResultsAngiopoietin-2 levels were elevated and fell with response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in PAH patients but didn’t change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. ConclusionsAngiopoietin-2 and D-dimer are elevated in PAH patients and may add prognostic information to routine clinical assessment.

Endothelial dysfunction markers syndecan-1 and thrombomodulin are associated with higher albuminuria levels in type 2 diabetes with no history of clinical cardiovascular disease

IntroductionIndividuals with type 2 diabetes and increased albuminuria, a well-established marker of microvascular complications, are at a higher risk for cardiovascular disease (CVD) and premature mortality. Therefore, a better understanding of the underlying pathophysiology is needed to improve risk stratification and tailor prevention and intervention. MethodsWe conducted a cross-sectional study including 463 individuals with type 2 diabetes, various degrees of albuminuria and without CVD. We analysed the association between albuminuria and markers of endothelial function (thrombomodulin and syndecan-1), thrombin generation (thrombin-antithrombin complex, prothrombin fragment 1 + 2), fibrinogen, platelet function (activation using soluble plasma selectin and aggregation using Multiplate® Analyzer) using regression models. ResultsIn the study cohort 33 % were women, the mean ± SD age was 65 ± 9 years, and median [IQR] diabetes duration was 15 [9–20] years. In total, 344 (74 %) individuals had normal albuminuria, 87 (19 %) moderately- and 32 (7 %) severely increased albuminuria levels. Higher markers of endothelial function and fibrinogen were independently associated with higher albuminuria levels (p < 0.01). No association between albuminuria and markers of thrombin generation and platelet was demonstrated. ConclusionWe demonstrated an independent association between albuminuria and markers of endothelial function and fibrinogen in individuals with type 2 diabetes and no history of CVD.

The Relation of Insulin Resistance With Free Androgen Index and Endothelial Dysfunction Marker YKL-40 and Its Effect on Male Infertility: A Prospective Study

The Relation of Insulin Resistance With Free Androgen Index and Endothelial Dysfunction Marker YKL-40 and Its Effect on Male Infertility: A Prospective Study

Pathophysiological Markers of Acute Respiratory Distress Syndrome Severity Are Correlated With Ventilation-Perfusion Mismatch Measured by Electrical Impedance Tomography.

Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch. Prospective observational study. General ICU of a university-affiliated hospital. Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation. Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers. Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure (r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph (r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue (r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan. In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.

New risk factors and predictions of the development of retinal vein occlusion after cardiac surgeries with the use of artificial circulation

Background. Cardiovascular diseases are one of the risk factors for the development of retinal vein occlusion (RVO). Cardiac interventions with artificial circulation (AC) can be associated with perioperative complications, including retinal vessel occlusion. The actual task of modern ophthalmology is to determine the frequency of retinal vessel occlusions, clinical features, risk factors, the role of markers of inflammation and endothelial dysfunction in RVO in patients with cardiovascular diseases after surgeries with artificial circulation. The purpose of the study was to investigate new risk factors and predict the development of retinal vein occlusions after cardiac surgeries using artificial circulation. Materials and methods. Three hundred and ninety-four patients (638 eyes) were under observation. Of them, 220 people (405 eyes) had cardiovascular diseases and underwent heart surgeries with the use of AC. In these patients, we determined the nature, frequency and features of the development and clinical course of RVO after cardiac surgery with AC in the early and late periods of observation (3 and 6 months). Also, a study was conducted of 174 patients (233 eyes) with cardiovascular diseases who underwent cardiac surgeries with AC, and the serum levels of markers of inflammation (IL-6 and IL-8) and endothelial dysfunction (VE-cadherin) were determined before and after operations depending on the time of RVO occurrence. The main group included 126 patients (137 eyes) who were diagnosed with occlusion of the central retinal vein (CRV) or its branches after surgery with AC; the comparison group — 43 patients (86 eyes) who did not have retinal vein occlusion during the entire observation period; the control group — 5 patients (10 eyes) who had the same degree and duration of the underlying disease, indications for surgery with AC, but were examined before the operation, and within 180 days after it, and did not have RVO. The patients were examined by an ophthalmologist 2, 7, 30, 60, 90 and 180 days after cardiac surgery. The content of IL-6, IL-8 and VE-cadherin in blood serum was determined by the enzyme immunoassay (Bender MedSystems, Austria). Statistical data were processed using the Statistica 10 program (StatSoft Inc., USA), regression analysis was performed with the help of the GLZ software package. Results. As a result of the research, it was found that the frequency of retinal vein occlusions after cardiac surgeries with the use of artificial circulation was 0.99 % on the 2nd day, 3.95 % on the 7th day, 10.2 % after 3 months, 1.4 % after 6 months. The conducted discriminant analysis showed that the type of occlusion was determined by age, lower visual acuity, and the order of occlusion of the CRV branches. An increase in the macular volume of the retina was also significant, reflecting the development of macular edema. The regression model for predicting the type of occlusion based on visual acuity, the order of occlusion of the CRV branches and age had a prediction accuracy of 82.5 %. Cardiac surgeries with the use of AC caused an increase in interleukin content in the early period (IL-6 on days 2 and 7, and IL-8 — up to day 30), while the content of VE-cadherin was slightly increased during almost the entire observation period. In the presence of RVO, IL-6 content was significantly higher at all stages of occlusion development, IL-8 content — up to 30 days, and VE-cadherin content — mostly after 7 days. Regression analysis showed that after 1–2 days, the occurrence of RVO was directly related to the content of IL-6 and IL-8 in the blood, on days 3–7 — to the content of only IL-8, on days 8–30 — to the content of all markers, and later — to the content of IL-6 and VE-cadherin. The prediction accuracy for the presence or absence of RVO in the corresponding term according to the calculated regression models is at least 78 % (p &lt; 0.001), which proves the influence of markers on the development of RVO. Conclusions. The conducted study shows the importance of acute inflammation and endothelial dysfunction in the occurrence of RVO when using AC, which justifies the use of preventive measures in the early stages of limiting the activity of the inflammatory process, in the later stages — preventing the development of endothelial dysfunction.

Occlusive lesions of retinal vessels: etiological and patogenetic factors

Background. Vascular pathology of the organ of vision is one of the most urgent problems of ophthalmology, as it is the main cause of vision loss and vision loss. Retinal vein occlusion ranks second after diabetic retinopathy in the world among vascular causes of vision loss. In a significant risk group for the occurrence of occlusions of the retinal vessels are patients with cardiovascular diseases. Today, treatment of patients with coronary heart disease and patho­logy of heart valves is impossible without surgical interventions, most of which require the use of artificial circulation (AC). During the operation of the AC due to prolonged hypothermia, hemodilution, prolonged hypotension, anemia, development of ophthalmologic complications in the early postoperative period is possible. The purpose of the study was to investigate etiological and pathogenetic factors of occlusive lesions of retinal vessels. Mate­rials and methods. The search for sources of Ukrainian and foreign literature for the ana­lytical review was conducted keywords using the open medical scientific database PubMed (USA). At the first stage, 211 sources were selected, of which 66 were selected for this article. Results. Occlusion of the central retinal vein (CVO) deve­lops in 214 people per 100,000 population, mainly in people over 65 years of age. The frequency of branh retinal vein occlusions (BRVO) is 67.2%, of which 82.4% is a occlusion of the superior temporal branch. The main risk factors of CVO are age, hypertension, diabetes, atherosclerosis, glaucoma, coronary heart disease. A small number of sources are found in the literature regarding complications from the organ of vision in patients after cardiac surgery with AC such us thromboembolism of retinal vessels, optic ischemic optic neuropathy, retinal ischemia, optic nerve atrophy, retinal detachment, proliferative vitreoretinopathy. The authors' research showed a multiple increase in blood markers of endothelial dysfunction, including vascular endothelial cadherin (VE-cadherin, VE-C) after surgery. Conclusions. Diseases of the organ of vision due to general or local blood circulation disorders account for 10 to 28%, 2.6% of which lead to blindness. There is a relationship between occlusive lesions of retinal veins and cardiovascular diseases. The main reasons for the development of retinal vein occlusion after cardiac surgery with coronary artery disease are acute inflammation occurring during and immediately after surgery and endothelial dysfunction.

Dynamics of endothelial function in patients with arterial hypertension with different cardiovascular risk against the background of antihypertensive therapy

The aim of the work was to investigate the dynamics of endothelial markers in patients with arterial hypertension with different cardiovascular risk under the influence of the prescribed treatment during a year of observation. The first group (with a moderate risk of cardiovascular events) included 48 patients with arterial hypertension (AH). The second group consisted of 54 patients with hypertension and a high risk of cardiovascular events, namely type 2 diabetes. Each group of patients was randomized into two subgroups by blood pressure (BP) medication. In patients of subgroup 1a (n=29) and subgroup 2a (n=35) – the main subgroups – the therapy necessarily included the angiotensin II receptor antagonist losartan potas­sium in a dosage of 50-150 mg/day, depending on the blood pressure level. Patients of subgroup 1b (n=19) and subgroup 2b (n=19) – comparison subgroups were treated with antihypertensive drugs of other first-line groups according to the data of the unified clinical protocol for the treatment of hypertension. According to the ROC analysis, it was determined that the dynamics of endothelin-1 (ET-1) indicators after 9 and 12 months of therapy (a decrease of 12% or more from the initial level) can predict the normalization of indicators of the coagulation and anticoagulation systems with indicators of sensitivity and specificity – 85% (95% CI 62.1-96.6%) and 92.9% (95% CI 76.5-98.9%), respectively. A decrease in the level of Willebrand factor (fV) by 23% or more due to such a treatment time can be used as a prognostic sign in determining the regression of endothelial dysfunction with sensitivity – 75% (95% CI 50.9-91.2%), specificity – 100% (95% CI 87.5-100%). According to the given data, both in the group with moderate and with high cardiovascular risk, there is a relationship between endothelial dysfunction (ED) and the duration of hypertension, indicators of the lipid spectrum and abdominal obesity – factors that increase the viscous resistance of the blood circulation, as well as platelet hyperactivity in the bloodstream. We have also established that according to the dynamics of ET-1 indicators after 9 and 12 months of therapy (decrease by 27% or more from the initial level), it is possible to predict the normalization of indicators of the coagulation and anticoagulation systems with indicators of sensitivity – 81.8% (95% CI 59.7-94.7%), specificity – 90.6% (95% CI 75-97.9%). A decrease in the level of fV by 24.5% or more after a year of treatment can be used as a prognostic sign in determining the regression of endothelial dysfunction with sensitivity – 68.2% (95% CI 45.1-86.1%), specificity – 71.9% (95% CI 53.3-86.2%). The obtained results testify to the dominant role of type 2 diabetes as a factor in platelet disorders of hemostasis. Taking into account the positive dynamics of the above-mentioned markers of ED during the year of treatment, their relationship with the reduction of blood pressure, indicators of the lipid spectrum and abdominal obesity, it should be noted the positive effect of angiotensin II receptor blockers (BRA II) as endothelioprotective drugs. Considering the irrefutable literary data about the absence of thrombomodulin in the blood stream, even its insignificant appearance indicates the presence of endothelial dysfunction. Determining the state and dynamics of changes in endothelial function under the influence of prescribed therapy will make it possible to improve the diagnosis of endothelial function disorders and increase the effectiveness of treatment of patients with hypertension and various cardiovascular risks.

Prognostic Significance of Markers of Endothelial Dysfunction in Case of Severe Combined Blunt Abdominal Trauma

INTRODUCTION. In case of polytrauma, an imbalance occurs between substances produced by the endothelium, the rheological properties of the blood are disrupted, the content of procoagulants increases, the permeability of the vascular wall increases, which contributes to thrombus formation and increased tissue hypoxia, and subsequently to the development of multiple organ failure, and, of course, affects the course of traumatic disease, the development of complications and mortality. However, specific markers of endothelial dysfunction and their levels, by which it is possible to reliably predict the course of traumatic disease in severe combined closed abdominal trauma for the appropriate pathogenetic treatment have not yet been determined.AIM OF THE STUDY. To determine the significance of some markers of endothelial dysfunction (C-reactive protein, von Willebrand factor, the number of desquamated endothelial cells in the blood) in combined blunt abdominal trauma to predict the likelihood of complications and adverse outcomes.MATERIAL AND METHODS. The main group consisted of 31 patients with severe combined blunt abdominal trauma, the comparison group consisted of 5 patients operated on for large ventral hernias. All patients underwent blood tests for C-reactive protein, von Willebrand factor, the number of desquamated endothelial cells.RESULTS. The level of all three considered markers of endothelial dysfunction in severe abdominal trauma significantly differs from that in operated non-traumatized patients, which allows differential diagnostics to be made between abdominal wall contusion and damage to internal organs; extremely high values suggest an unfavorable course of traumatic disease and a high probability of a fatal outcome.CONCLUSION. Taking into account that the development of traumatic disease is based on damage to the vascular endothelium, it is necessary to consider as prognostic indicators changes in the level of activity of C-reactive protein, von Willebrand factor, desquamated endothelial cells in patients with severe combined blunt abdominal trauma.

The role of markers of endothelial dysfunction in the pathogenesis of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p &lt; 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p &lt; 0.001), whereas markers of endothelial dysfunction were not independent predictors. Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

Low-grade systemic inflammation in patients with long COVID: The role of imbalance of endotoxin-releasing systems and vasoconstrictor markers

Background. Currently, the pathophysiological mechanisms of acute damage to organs and systems caused by coronavirus infection have been studied quite fully, but the mechanisms underlying the clinical manifestations of long COVID have not yet been accurately described. The mechanisms of persistence of a number of symptoms in patients who have had COVID-19 and the role of systemic inflammation and endotoxemia markers in it remain a understudied aspect and a promising direction for further studying.The aim of the study. To assess the markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability and endothelial dysfunction in patients with long COVID at the stage of health resort treatment.Methods. The study included 32 patients who had recovered from coronavirus infection and were undergoing health resort treatment in the pulmonology department of the I.M. Sechenov Academic Research Institute for Physical Therapy, Medical Climatology and Rehabilitation. We also selected a control group (n = 20). All patients underwent peripheral blood analysis to detect the levels of markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability, endothelial dysfunction and vasoconstrictor agents: C-reactive protein (CRP), lipopolysaccharide-binding protein (LPB), tissue-type plasminogen activator (tPA), zonulin, bactericidal/ permeability-increasing protein (BPI), vasopressors of angiotensin 2 and endothelin (EDN1).Results. Patients who had recovered from coronavirus infection had a statistically significant increase in the levels of CRP (3.4 [2.56; 4.0] mg/l), LBP (18.46 [14.0; 25.5] ng/ml), tPA (0.07 [0.02; 0.32] ng/ml), angiotensin 2 (133.3 [63.0; 503.7] pg/ml) and a decrease in the level of BPI (1576 [276; 3588] pg/ml) (p &lt; 0.05).Conclusion. A statistically significant increase in markers of systemic inflammation, endotoxinemia, and vasoconstrictor agents in patients with long COVID indicates an imbalance in endotoxin-binding and endotoxin-releasing systems in patients who have had coronavirus infection. Further study of the described markers is necessary to improve approaches to long-term personalized therapy for this category of patients.

Endothelial Dysfunction in Children with Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome

Background Children with frequently relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS) show endothelial dysfunction and risk of endothelial injury during relapses, increasing the risk of accelerated atherosclerosis and adverse cardiovascular events. This study examines the plasma levels of markers of endothelial dysfunction [sE-selectin and vascular cell adhesion molecule-1 (VCAM-1)] in children aged 1–16 years with FRNS and SDNS in relapse. Materials and Methods Fifty-six children with FRNS and SDNS between 1 and 16 years were enrolled at the time of relapse and followed till six weeks of steroid-induced remission. Markers of endothelial dysfunction (sE-selectin and VCAM-1) in plasma were measured in these children and in an equal number of controls. Results Plasma sE-selectin and VCAM-1 levels were significantly raised during relapse, declined after six weeks of steroid-induced remission, and became comparable to controls (p &lt; 0.0001). We found high serum total cholesterol and triglycerides levels during relapse that remained elevated even after steroid-induced remission as compared to controls (p &lt; 0.0001). Raised levels of these markers confirm endothelial dysfunction in FRNS and SDNS patients. Conclusion Children with FRNS and SDNS had endothelial dysfunction during relapse, which was largely dependent upon disease activity.

P107 THE EFFECT OF MELDONIUM ON THE ENDOTHELIAL FUNCTION ASSESSED BY PLASMA ENDOCAN LEVEL IN PATIENTS WITH ESSENTIAL HYPERTENSION

Background and Objective: Endothelial dysfunction is one of the main findings in patients with arterial hypertension. It is associated with atherosclerosis initiation and progression. Lately, a soluble dermatan sulfate proteoglycan Endocan is used as a marker of endothelial dysfunction in patients with big variety of diseases. Hence, aim of our study was to assess effect of competitive inhibitor of carnitine-dependent fatty acid oxidation and promoter of anaerobic oxidation via the glycolytic pathway, Meldonium, on endothelial function in patients with arterial hypertension. Methods: 30 nonsmoker, non-obese male patients with stage II hypertension (ESH/ESC 2018) were involved in a study. 15 patients were put on recommended antihypertensive treatment plan and other 15 patients on conventional plus Meldoneum 1000 mg per day treatment for 3 months. Endocan level was tested before and after 3 months of treatment period. Hypertension was diagnosed as an average office blood pressure of three different visits equal or more than 140/90 mmHg. Written informed consent letters were obtained from all the participants. Results: Mean age and average blood pressure of study groups were not different between conventional and conventional plus Meldonium groups (48.6±6.94 vs 51.53±7.22 years old and 148/94 vs 151/95; P= NS for both). Initial plasma endocan level also was similar between the two groups (1.920±0.625 for Meldonium and 1.854±0.391 for conventional treatment; P=NS). In comparison with initial level, plasma endocan level significantly decreased after 3 months of treatment with conventional plus Meldonium treatment (1.920±0.625 vs 1.344±0.041; P&lt;0.05). Statistically significant difference of endocan level change after 3 month of treatment with conventional antihypertensive agents was not observed (1.854±0.391 vs 1.75±0.649; P=NS). Conclusion: Obtained results indicate, that 1 g/day Meldonium on top of conventional guideline recommended antihypertensive regimen significantly improves endothelial function assessed via plasma endocan level. Further studies are needed to confirm these results on a bigger population samples.

Endothelial Dysfunction in Youth-Onset Type 2 Diabetes: A Clinical Translational Study.

Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings. Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate. Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P=0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P<0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P=0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells. Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385.

Surrogates of Endothelial Injury Predict Survival After Post-transplant Cyclophosphamide

Post-transplant cyclophosphamide (PT-Cy) is becoming the standard of care for preventing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplant (alloHCT). Cyclophosphamide is associated with endothelial injury. We hypothesized that the endothelial activation and stress index (EASIX) score, being a marker of endothelial dysfunction, will predict non-relapse mortality (NRM) in alloHCT patients receiving PT-Cy for GVHD prophylaxis. We evaluate the prognostic ability of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and EASIX scores, and report other factors influencing survival, in patients with hematologic malignancies undergoing alloHCT and receiving PT-Cy-based GVHD prophylaxis. Adult patients with hematologic malignancies who underwent alloHCT and received PT-Cy for GVHD prophylaxis at the three Mayo Clinic locations were included in this study. We retrospectively reviewed the Mayo Clinic database and the available electronic medical records to determine the patient, disease, and transplant characteristics. An HCT-CI score of ≥3 was considered high. The EASIX score was calculated from labs available between day -28 (of alloHCT) to the day of starting conditioning and analyzed on log2 transformed values. A log2-EASIX score ≥2.32 was considered high. The cumulative incidence of NRM was determined using competing risk analysis, with relapse considered as competing risk. Overall survival (OS) from transplant was determined using Kaplan-Meier and log-rank methods. Cox-proportional hazard method was used to evaluate factors impacting survival. A total of 199 patients were evaluated. Patients with a high log2-EASIX score had a significantly higher cumulative incidence of NRM at 1 year after alloHCT (34.5% versus 12.3%, P = .003). Competing risk analysis showed that a high log2-EASIX score (HR 2.92, 95% CI 1.38 to 6.17, P = .005) and pre-alloHCT hypertension (HR 2.15, 95% CI 1.06 to 4.36, P = .034) were independently predictive of 1 year-NRM. Accordingly, we combined the two factors to develop a composite risk model stratifying patients in low, intermediate, and high-risk groups: 111 (55.8%) patients were considered low-risk, 76 (38.2%) were intermediate and 12 (6%) were high-risk. Compared to patients in the low-risk group, the intermediate (HR 2.38, 95% CI 1.31 to 4.33, P = .005) and high-risk (HR 5.77, 95% CI 2.31 to 14.39, P < .001) groups were associated with a significantly inferior 1-year OS. Multiorgan failure (MOF) was among the common causes of NRM (14/32, 43.8%) particularly among patients with prior pulmonary comorbidities [7 (50%) patients]. Our study shows that EASIX score is predictive of survival after PT-Cy. The novel EASIX-HTN composite risk model may stratify patients prior to transplant. MOF is a common cause of NRM in patients receiving PT-Cy, particularly among patients with pulmonary comorbidities.

Effects of Single Low-Carbohydrate, High-Fat Meal Consumption on Postprandial Lipemia and Markers of Endothelial Dysfunction: A Systematic Review of Current Evidence.

Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights. The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED. CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date. Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies. Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function. PROSPERO registration no. CRD 42023398774.

Abstract Tu017: MerTK inhibition aggravates partial carotid ligation-induced atherosclerosis

Introduction: Partial carotid ligation (PCL) is a widely used model to generate acute disturbed flow (d-flow) in left carotid artery (LCA), leading to rapid endothelial dysfunction and atherosclerosis formation. While the right carotid artery (RCA) without PCL is a built-in control characterized by steady flow (s-flow). Endothelial cells (ECs) form a single cell layer that is constantly exposed to blood flow patterns and play important roles in atherosclerosis. MER proto-oncogene tyrosine kinase (MerTK) is the major receptor for efferocytosis, a process of the efficient clearance of apoptotic cells. MerTK is mainly expressed in macrophages and there are very limited reports focusing on MerTK function in ECs. This study was designed to investigate the role of blood flow patterns in regulating MerTK expression in aortic ECs and its contributions to the development of atherosclerosis. Methods: Partial carotid artery ligation combined with AAV-PCSK9 and high fat diet (HFD) were used to set up acute atherosclerosis within 4 weeks with WT and MerTK -/- mice. Proteomics and molecular experiments were applied to reveal the potential mechanism pathways. Results: Our proteomics data showed that, compared with WT group, MerTK -/- aggravates atherosclerosis in LCA through upregulation of endothelial dysfunction markers (e.g. IL-1β, NF-κB, TLR4, MAPK signaling) and mitochondrial dysfunction. Our immunostaining data further validates the proteomics data, showing that MerTK -/- induces impaired endothelial efferocytosis and expression of endothelial dysfunction markers (e.g., Caspase-3, NF-κB, TLR4, vWF, VCAM-1, and P22 phox ) and promotes the development of atherosclerosis. Conclusion: Our data suggests that endothelial MerTK is sensitive to d-flow and determines endothelial efferocytosis in vivo. MerTK inhibition promotes endothelial dysfunction and atherosclerosis. Our data may provide novel evidence and reference opinions for the application of endothelial MerTK- targeted therapeutics to treat atherosclerosis.

Beyond troponins: Emerging diagnostic significance of novel markers in NSTEMI.

Objective: This study aims to comprehensively analyze a multiple-marker panel consisting of 55 morphofunctional and biochemical markers in 123 patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI). The goal of this study was to identify novel pathogenetic landmarks and diagnostic predictors associated with NSTEMI. Methods: The study includes 123 patients diagnosed with NSTEMI based on ESC Guidelines criteria. Clinical characteristics, morphofunctional markers, and serum levels of 53 biochemical markers related to inflammation, oxidative stress, endothelial dysfunction, cellular injury, hemostasis, and myocardial remodeling were assessed. A control group of 47 healthy individuals was included for comparison. Results: NSTEMI patients exhibited an activated inflammatory status, oxidative stress, and endothelial dysfunction. Notable increases in inflammation markers, alterations in adipokines, and changes in oxidative stress markers were observed. Endothelial dysfunction markers indicated vascular remodeling and dysfunction. Cellular injury markers, including cMyBP-C, suggested myocardial necrotic injury. Hemostasis markers showed impaired anticoagulant systems, and ECM remodeling markers indicated increased matrix metalloproteinases. Conclusion: The multiple-marker panel provides insights into novel pathogenetic entities associated with NSTEMI. Markers such as MPO, MMP-8, E-selectin, PhA2, Ang 2, FE, MF, and cMyBP-C demonstrate potential diagnostic and prognostic value. This comprehensive analysis enhances our understanding of NSTEMI pathogenesis and offers potential targets for therapeutic interventions.