Endothelial Dysfunction In Patients Research Articles

Correction of endothelial dysfunction in patients with type 2 diabetes mellitus, diabetic kidney disease and non-alcoholic steatohepatitis

Background. Non-alcoholic fatty liver disease and chronic kidney disease are public health concerns worldwide due to their increasing prevalence, adverse prognosis, and health care burden. The purpose of the study was to determine the probable effect of a combination of metformin, rosuvastatin, essential phospholipids and quercetin on the blood lipids, endothelial function, fibrinolysis system and platelet hemostasis, which are factors for the progression of nonalcoholic steatohepatitis. Materials and methods. Studies were performed on the dynamics of treatment in 60 patients with non-alcoholic fatty liver disease, type 2 diabetes mellitus and diabetic kidney disease (stage I–III). Depending on the prescribed treatment at random, the examined patients were divided into 2 groups. Twenty-eight persons of the first group received a low-calorie diet with dietary restrictions, essential phospholipids, metformin hydrochloride, rosuvastatin. Thirty-two patients from the second group received quercetin in addition to similar dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy. The mean age of patients was 53.80 ± 3.52 years. The comparison group consisted of 30 healthy individuals of the corresponding age. Results. To evaluate the degree of endothelial-protective effect of quercetin on the background of the recommended protocol therapy, markers of endothelial dysfunction, fibrinolysis and platelet hemostasis were studied. NO content significantly reduced (1.7 times) in patients of group 2 before treatment, increased by 1.5 times (p < 0.05). This can be explained by the effect of quercetin, as well as the use of metformin, which reduces the degree of insulin resistance and the level of hyperlipidemia. Conclusions. The effectiveness of a combination therapy for non-alcoholic steatohepatitis and type 2 diabetes mellitus with diabetic kidney disease using essential phospholi­pids, statins and metformin with the addition of quercetin is higher than that of traditional therapy, as it significantly restores the functional state of the endothelium, eliminates the phenomena of hypercoagulation syndrome without the additional prescription of antiplatelet agents.

Recovery of Smell and Taste in Patients With Persistent COVID-19-Related Hyposmia and Dysgeusia by Targeting Inflammation and Endothelial Dysfunction.

Purpose New-onset loss of olfaction and/or taste is now recognized among the hallmark symptoms of COVID-19. In most patients, these symptoms resolve completely and spontaneously within days. However, some patients experience persistent olfactory and gustatory dysfunction after COVID-19 resolution. We evaluated the efficacy of a treatment combining several therapeutic agents to target inflammation and endothelial dysfunction in patients with persistent hyposmia and dysgeusia. Methods This 12-month observational pilot study involved patients presenting with symptoms of hyposmia and dysgeusia 30 days after COVID-19 had subsided. The main objective was to evaluate the efficacy of a combination of systemic corticosteroids, a glycosaminoglycan (GAG)-based antithrombotic (mesoglycan), a diuretic, and a vitamin complex. The perceived extent of olfaction and taste impairment was assessed using an 11-point visual analog scale (VAS), where 0 = complete loss of olfaction/taste and 10 = complete recovery of olfaction/taste. Results Eighty-seven patients with post-COVID-19 hyposmia and dysgeusia were enrolled. At treatment start (T0), the mean VAS scores were 2.0 and 3.2 for olfactory and gustatory functions, respectively. Both functions appeared to improve progressively and significantly from T0 to 12 months. A shorter time between viral infection and the start of treatment was associated with a more pronounced recovery of both senses. Conclusions Combined systemic corticosteroid, GAG-based antithrombotic agent (mesoglycan), and diuretic may constitute an option for treating persistent hyposmia and dysgeusia associated with COVID-19. To ensure optimal recovery, early treatment start is recommended. The described treatment protocol deserves to be further evaluated.

Circulating endothelial cells – as an indicator of endothelial dysfunction in patients with miocardial infarction

Aim. To assess the state of the vascular endothelium in patients with myocardial infarction in terms of desquamated endotheliocytes before and after treatment.Material and methods. The results of morphological study of 30 patients with coronary heart disease: post infarction cardio sclerosis and 20 healthy volunteers are presented for comparison with the mean age of 65,1±3,6 and 62,7±3,7 years, respectively. In order to determine the number of DECs, we used the morphological method proposed by N.N. Petrishcheva et al. (2001), before and after impatient treatment.Results. Statistically significant DEC parameters were obtained in patients with myocardial infarction. The highest rates of DEC were found in 10% of patients (19±0,1×104 cells/l). Most patients (53.33%) had a moderate level of endotheliocytemia (11,2±0,7×104 cells/l). The control group, taken for comparison, had the upper limits of the physiological norm (3,9±0,9×104 cells/l). This shows a significant role of endothelial dysfunction in the pathogenesis of myocardial infarction. A group of patients who had up to 10 years of a heart attack history revealed a direct correlation with the level of DEC.Conclusion. The number of DECs was significantly increased in patients with myocardial infarction compared with the control group before treatment. Against the background of complex therapy, the level of endotheliocytemia is significantly reduced, but does not reach physiological parameters.

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post-hoc analysis of the PROCEED trial.

To analyse the changes in erythropoietic and estimated fluid volume parameters after the initiation of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This was a post-hoc analysis of the PROCEED trial, which evaluated the effect of 24-week ipragliflozin treatment on endothelial dysfunction in patients with T2DM and CKD. We evaluated the changes in erythropoietic and estimated fluid volume parameters from baseline to 24 weeks post-treatment in 53 patients who received ipragliflozin (ipragliflozin group) and 55 patients with T2DM and CKD without sodium-glucose co-transporter 2 inhibitors (control group), a full analysis set of the PROCEED trial. The increases in haemoglobin [estimated group difference, 0.5 g/dl; 95% confidence interval (CI), 0.3-0.8; p < .001], haematocrit (estimated group difference, 2.2%; 95% CI, 1.3-3.1; p < .001) and erythropoietin (estimated log-transformed group difference, 0.1; 95% CI, 0.01-0.3; p = .036) were significantly greater in the ipragliflozin group than those in the control group. Ipragliflozin treatment was significantly associated with an increase in erythropoietin, independent of the corresponding change in haemoglobin (β = 0.253, p < .001) or haematocrit (β = 0.278, p < .001). Reductions in estimated plasma volume (estimated group difference, -7.94%; 95% CI, -11.6 to -4.26%; p < .001) and estimated extracellular volume (estimated group difference, -181.6 ml; 95% CI, -275.7 to -87.48 ml; p < .001) were significantly greater in the ipragliflozin group than those in the control group. Erythropoiesis was enhanced and estimated fluid volumes were reduced by ipragliflozin in patients with T2DM and CKD. PROCEED trial (registration number: jRCTs071190054).

The role and mechanism of RIPK1 in vascular endothelial dysfunction in chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and cardiovascular events, but the mechanism is unclear. In our study, we found elevated levels of RIPK1 in patients with CKD and cardiovascular events through bioinformation analysis. Elevated RIPK1 levels were found in serum samples of CKD patients and were associated with vascular endothelial dysfunction and renal function. We constructed the five of six nephrectomy of CKD mice model, finding that RIPK1 expressions were elevated in abdominal aorta endothelial cells. After RIPK1 inhibition and overexpression, it was found that RIPK1 could regulate the expression of endothelial nitric oxide synthase (eNOS) and cell adhesion molecule 1 (ICAM-1), and activation of inflammatory responses and endoplasmic reticulum (ER) stress. In addition, uremic toxin induced abnormal expression of RIPK1 invitro. We observed RIPK1-mediating endothelial dysfunction and inflammation responses by ER stress pathways through gain and loss of function. In order to explore the specific mechanism, we conducted co-immunoprecipitation and expression regulation of RIPK1 and IKK, finding that RIPK1 formed complex with IKK and regulated IKK expression. In conclusion, we demonstrated that RIPK1 levels were closely associated with vascular endothelial dysfunction in patients with CKD. With uremic toxins, RIPK1 expression was elevated, which led to the activation of inflammation through the ER stress pathway, resulting in vascular endothelial injury. Besides, activation of RIPK1-IKK-NF-κB axis was a key driver of endothelial dysfunction in CKD. Our study provides a new perspective for the study of cardiovascular events in CKD.

Association between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease.

Endothelial dysfunction is a systemic disorder and risk factor for atherosclerosis. Our aim was to assess whether there is a relation between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease (CAD). We prospectively studied 54 patients, who had a positive result for obstructive CAD in coronary CT angiography. Myocardial perfusion (15O)H2O positron emission tomography was imaged at rest and during adenosine-induced maximal vasodilation. Peripheral endothelial function was assessed by measuring flow-mediated dilation (FMD) with ultrasound from the left brachial artery. There was a statistically significant correlation between FMD and global hyperaemic myocardial blood flow (MBF; r = 0.308, P = 0.023). The correlation remained statistically significant when controlling for gender, height, and diastolic blood pressure at rest (r = 0.367, P = 0.008). Receiver operating character analysis, however, yielded an area under curve of only 0.559 (P = 0.492) when FMD was used to predict reduced MBF (below 2.3 mL/g/min). Patients with significantly decreased MBF (n = 14) underwent invasive coronary angiography. FMD showed an inverse correlation with the severity of the most significant stenosis (r = -0.687, P = 0.007). Peripheral endothelial function is related with hyperaemic MBF and with the severity of CAD in invasive coronary angiography. Due to insufficient sensitivity and specificity in the identification of reduced MBF, FMD is not suitable for clinical practice at the individual level. However, it works at the population level as a research tool when assessing endothelial dysfunction in patients with CAD.

Association between Relative Thrombocytosis and Microalbuminuria in Adults with Mild Fasting Hyperglycemia.

An elevated platelet count may contribute to significant thrombotic events and pose a risk for diabetic microvascular complications. Albuminuria, one of the hallmarks of diabetes, is thought to be a risk factor for endothelial dysfunction. In this study, we investigated the association between relative thrombocytosis and an increased urine albumin-to-creatinine ratio in healthy adult participants. Using multivariate analyses on data from the Korea National Health and Nutrition Examination Survey V-VI, 12,525 eligible native Koreans aged ≥ 20 were categorized into platelet count quintiles by sex. The highest platelet count quintile included younger, more obese participants with elevated white blood cell counts, poor lipid profiles, and a better estimated glomerular filtration rate. Restricted cubic spline regression analysis revealed significant associations between platelet count and fasting blood glucose, glycated hemoglobin, and urine albumin-to-creatinine ratio. Adjusted logistic regression models indicated that heightened fasting blood glucose and platelet count were linked to risk of microalbuminuria (fasting blood glucose, odds ratio = 1.026, 95%CI = 1.011-1.042; platelet count, odds ratio = 1.004, 95%CI = 1.002-1.006). Particularly, an increased platelet count was notably associated with microalbuminuria progression in subjects with impaired fasting glucose. These findings suggest that an elevated platelet count, even below diagnostic thrombocytosis levels, independently correlates with an increased risk of vascular endothelial dysfunction in patients with impaired fasting glucose.

Association of Monocyte-to-HDL Cholesterol Ratio with Endothelial Dysfunction in Patients with Type 2 Diabetes.

To explore the relationship between monocyte-to-HDL cholesterol ratio (MHR) and endothelial function in patients with type 2 diabetes (T2DM). 243 patients diagnosed with T2DM were enrolled in this cross-sectional study. Patients were divided into two groups by flow-mediated dilation (FMD) quintile as nonendothelial dysfunction (FMD ≥ 6.4%) and endothelial dysfunction (FMD < 6.4%). The relationship between MHR and FMD was analyzed using Spearman's correlation, partial correlation, and multiple logistic regression analysis. ROC curve was fitted to evaluate the ability of MHR to predict endothelial dysfunction. Endothelial dysfunction was present in 193 (79%) patients. Patients with endothelial dysfunction had higher MHR (p < 0.05) than those without endothelial dysfunction. Furthermore, MHR had a significantly positive correlation with endothelial dysfunction (r = 0.17, p < 0.05), and the positive association persisted even after controlling for confounding factors (r = 0.14, p < 0.05). Logistic regression showed that MHR was an independent contributor for endothelial dysfunction (OR: 1.35 (1.08, 1.70), p < 0.05) and the risk of endothelial dysfunction increases by 61% with each standard deviation increase in MHR (OR: 1.61 (1.12, 2.30), p < 0.05) (model 1). After adjusting for sex, age, BMI, disease course, hypertension, smoking, and drinking (model 2) as well as HbA1c, HOMA-IR, C-reactive protein, and TG (model 3), similar results were obtained. In ROC analysis, the area of under the ROC curve (AUC) for MHR was 0.60 (95% CI 0.52-0.69, p < 0.05). MHR was independently associated with endothelial dysfunction in T2DM patients. It could be a new biomarker for vascular endothelial function assessment.

Endothelin-1 indices in patients with leptospirosis of various severity degrees and their changes under the influence of seven-day treatment

Introduction. Leptospirosis is one of the most common zoonoses in the world, pathogenesis of which is based on the damage of vascular endothelium. Violation of endothelial functions leads to damage of these cells plasma membranes, loss of vascular integrity, ischemia, necrosis, and, finally, the development of organ dysfunction. In current literature there is sparce information concerning endothelial dysfunction in patients with leptospirosis, therefore the development and standardization of methods for the assessment of vascular endothelium imbalance in patients with leptospirosis of different severity degrees is an urgent task. Detection of endothelin-1 (ET-1) one of the best markers of endothelial dysfunction, can become an important tool for predicting the severity of the disease. The aim of the study. To investigate ET-1 indices in patients with leptospirosis of different severity degrees and to estimate their changes after the seven-day treatment. Materials and methods. ET-1 content in the blood serum of patients with diagnosed leptospirosis was detected by ELISA method. Absolute values were compared using Mann-Whitney test (U-test); the results were statistically processed using Fisher’s bilateral test (F-test). Correlation analysis was carried out according to Spearman’s method. The difference was considered statistically significant with p less than 0.05. Results. ET-1 content was detected at time of hospitalization and after 7 days of leptospirosis treatment. Patients (n = 43) were divided into two groups depending on the severity of leptospirosis course: the first group with a moderate course included 21 patients; second group with a severe course included 22 patients; the control group consisted of 20 healthy individuals. Both groups of leptospirosis affected patients demonstrated significantly higher ET-1 concentration in comparison with the control group (p less than 0.01). Moreover, the proportion of patients with high (more than 5.5 pg/ml) concentration of ET-1 in the blood post the 7 days treatment was documented in 13.3% patients of the first group, and 43.8 % patients of the second group (p less than 0.05). It was also estimated that in both groups patients 7 days treatment of leptospirosis induced a credible increase in the concentration of ET-1 (p less than 0.05). Conclusions. Our results claim that at time of hospitalization and after 7 days treatment both groups of leptospirosis affected patients demonstrated significantly higher level of ET-1 in comparison to control group individuals (p less than 0.01). 7 days of leptospirosis treatment caused a credible enhancement of ET-1 content (p less than 0.05). Patients with a severe course of leptospirosis after 7 days treatment exposed significantly higher ET-1 concentration compared to patients with moderate course (p less than 0.05).

Эндотелиальная дисфункция у пациентов с коронавирусной инфекцией COVID-19

Endothelial dysfunction is the main cause of thrombotic complications and unfavorable disease outcome in COVID-19. The study of markers of endothelial dysfunction in patients with COVID-19 will help to determine additional directions for the treatment of hemostatic disorders. The purpose — to evaluate the diagnostic significance of endothelial dysfunction markers in moderate and severe forms of COVID-19. Material and methods. The study was carried out in 28 patients with COVID-19 hospitalized at the Republic Clinical Infectious Diseases Hospital (Kazan) from 02.16.2023 to 03.07.2023. The median age of patients was 66.5 years. The control group consisted of 20 healthy people of the same age. Results. It was found that moderate and severe forms of COVID-19 are accompanied by increased values of D-dimer and VWF in the blood, the medians of which were 2.6 and 1.9 times higher than control values, respectively. No significant differences in the values of P-selectin and thrombomodulin were detected in the compared groups. A moderate correlation was established between the level of P-selectin and the absolute number of neutrophils in the blood. It was found that the values of D-dimer and thrombomodulin were significantly higher in patients with COVID-19 who had two or more comorbid diseases. The high likelihood ratios of FFB and D-dimer positivity (LR+ = 8.4) allow considering them as reliable parameters for assessing endothelial dysfunction in patients with COVID-19. Conclusion. Endothelial dysfunction in COVID-19 disease is manifested by increased levels of D-dimer and VWF in the blood. The identified changes indicate the possibility of using medications that neutralize VWF in addition to anticoagulant drugs.

Investigation of the Relationship Between Left Ventricular Hypertrophy and Endothelial Dysfunction in Patients with Primary Hypertension by ADMA and hsCRP

Investigation of the Relationship Between Left Ventricular Hypertrophy and Endothelial Dysfunction in Patients with Primary Hypertension by ADMA and hsCRP

Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

Endothelial Dysfunction is Related to Central Retinal Artery Occlusion

Objective: Central retinal artery occlusion (CRAO) is severe and painless vision loss due to retinal infarction. Most CRAO patients have atherosclerotic risk factors. Flow-mediated dilatation (FMD) and pulse wave velocity (PWV) may indicate the presence or progression of atherosclerosis. This study aims to evaluate the arterial stiffness parameters and the presence of endothelial dysfunction in patients with CRAO. Materials and Methods: 33 consecutive CRAO patients (63 ± 7 years, 21 men (63.6%)) were recruited in the study. 35 age /sex-matched participants were included as a control group, FMD and PWV were measured from the brachial artery, as indicators of endothelial dysfunction and atherosclerosis in the arterial wall, respectively. Additionally, the transthoracic echocardiographic parameters of the patients were investigated. Results: CRAO patients had significantly higher frequencies of hypertension, hyperlipidemia, and smoking status. Furthermore, the frequency of diabetes was also higher in the CRAO group, but the difference was not statistically significant. CRAO patients had significantly higher PWV and lower FMD compared to the controls. There were no significant differences between groups regarding left ventricle systolic and diastolic functions. Conclusion: Our study showed that CRAO patients may have endothelial dysfunction and increased arterial stiffness. Systemic endothelial dysfunction and atherosclerosis may be linked to the development of CRAO.

Некоторые маркеры эндотелиальной дисфункции у пациентов с артериальной гипертензией с сочетанной патологией

Некоторые маркеры эндотелиальной дисфункции у пациентов с артериальной гипертензией с сочетанной патологией

Type I Interferons induce endothelial destabilization in Systemic Lupus Erythematosus in a Tie2-dependent manner.

Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and Tie2 is a receptor essential for vascular stability. Inflammatory processes promote inhibition of Tie2 homeostatic activation, driving vascular dysfunction. In this work we determined whether type I Interferons (IFN) induce Tie2 signalling-mediated endothelial dysfunction in patients with SLE. Serum levels of Angiopoietin (Ang)-1, Ang-2 and soluble (s)Tie1 in patients with SLE and healthy controls were measured by ELISA. Monocytes from patients with SLE and Human Umbilical Vein EC (HUVEC) were stimulated with IFN-α, IFN-β (1000 I.U.) or SLE serum (20%). mRNA and protein expression, phosphorylation and translocation were determined by quantitative PCR, ELISA, Western Blot, flow cytometry and confocal microscopy. Viability and angiogenic capacity were determined by calcein and tube formation assays. We found that sTie1 and Ang-2 serum levels were increased and Ang-1 decreased in patients with SLE and were associated with clinical characteristics. Type I IFN significantly decreased Ang-1 and increased Ang-2 in monocytes from patients with SLE. Type I IFN increased sTie1 and Ang-2 secretion and reduced Tie2 activation in HUVEC. Functionally, type I IFN significantly reduced EC viability and impaired angiogenesis in a Tie2 signalling-dependent manner. Finally, SLE serum increased Ang-2 and sTie1 secretion and significantly decreased tube formation. Importantly, Tie1 and IFNAR1 knockdown reversed these effects in tube formation. Overall, type I IFN play an important role in the stability of EC by inhibiting Tie2 signalling, suggesting that these processes may be implicated in the cardiovascular events observed in patients with SLE.

Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD=1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD=0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Endothelial dysfunction in postoperative purulent-septic complications of hepatobiliary zone pathologies

Objective. Determination of the significance of endothelial dysfunction in postoperative purulent-septic complications of pathologies of the hepatobiliary zone.Material and methods. An analysis was conducted on 57 patients who underwent surgery for pathologies of the hepatobiliary zone and subsequently developed postoperative purulent-septic complications. Among these, there were 17 cases of postoperative peritonitis, 20 cases of postoperative intra-abdominal abscesses, and 20 cases of postoperative pancreatic necrosis. Of the patients, 19 were men (33.3%), and 38 were women (66.7%). Their ages ranged from 20 to 71 years.Results. Out of the 57 patients, when classified based on the severity of endotoxemia: 26.3% had a mild degree, another 26.3% had a moderate degree, 15% had a severe degree, and 21.0% had an extremely severe degree. High levels of oxidative stress markers and decreased SOD levels were particularly evident in patients with postoperative intra-abdominal abscesses. Furthermore, even greater acceleration of lipid peroxidation processes was observed in patients with severe endotoxemia resulting from widespread postoperative peritonitis and extensive to nearly total postoperative pancreatic necrosis. Additionally, significant changes were noted in endotoxemia predictors in portal blood, endothelial dysfunction markers, and cytokines in patients with postoperative intra-abdominal purulent-septic complications.Conclusion. Endothelial dysfunction in patients with postoperative purulent-septic complications is associated with profound pathomorphological changes in hepatocytes. These changes are evident in alterations to rheology, microcirculation, and increased levels of endothelial dysfunction markers.

Abstract 13824: Salsalate Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Background: Insulin resistance accelerates systemic inflammation and vascular dysfunction. Salsalate suppresses inflammation and may improve insulin sensitivity and insulin-mediated, endothelium-dependent vasodilation. Hypothesis: We hypothesized that salsalate treatment would improve insulin-stimulated forearm blood flow (FBF) in volunteers with metabolic syndrome compared to placebo. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00760019) evaluating 4-weeks of salsalate 1.5 grams TID on insulin-stimulated FBF during an insulin clamp in patients with and without metabolic syndrome. Results: Nineteen patients received salsalate (13 metabolic syndrome and 6 healthy controls). Patients with metabolic syndrome were older (36.3 vs 57.1 years old, p=0.002) with higher BMIs (33.9 vs 25.5 kg/m 2 , p=0.001) and higher insulin levels (10.8 vs 4.3 μU/mL, p=0.01). Those with metabolic syndrome had impaired insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR, 2.66 vs 0.87, p=0.005) and Matsuda Index (MI, 5.81 vs 3.32, p=0.001). After salsalate treatment, insulin sensitivity was unchanged (Panel A &amp; B) and there was no significant reduction in insulin levels (Panel C) or inflammation by C-reactive protein (Panel D). Insulin stimulation increased FBF in patients treated with placebo (p=0.012) and salsalate (p=0.003), but salsalate blunted the FBF response in those with metabolic syndrome (p=0.022, Panel E). In multivariable linear regression, metabolic syndrome, HOMA IR, and MI associated with insulin-stimulated FBF independent of salsalate treatment. Conclusion: Salsalate improved neither insulin sensitivity nor systemic inflammation, and it blunted insulin-stimulated vasodilation in patients with metabolic syndrome. Salsalate does not modulate systemic inflammation and worsens arteriolar endothelial dysfunction in patients with metabolic syndrome.

Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction.

obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA. This case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits. miR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls. Circulating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.

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