Endothelial Dysfunction In Patients Research Articles

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<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.

Transcatheter aortic valve implantation and its impact on endothelial function in patients with aortic stenosis

Vascular function is impaired in patients with aortic valve stenosis (AS). The impact of transcatheter aortic valve implantation (TAVI) on endothelial function is inconclusive so far. Therefore, we sought to assess the short-term influence of TAVI on endothelial dysfunction in patients with AS.We recruited 47 patients (76.6 % male, 80.04 years old) with AS scheduled for TAVI. Endothelial function was assessed by fingertip reactive hyperemia peripheral arterial tonometry (RH-PAT). Measurements were conducted one day before and three days after TAVI. Patients were grouped according to RH-PAT change after TAVI.Overall, RH-PAT measurements did not significantly improve after TAVI (Reactive Hyperemia Index: 1.5 vs 1.6, p = 0.883; logarithm of the Reactive Hyperemia Index: 0.44 vs. 0.49, p = 0.523). Interestingly, patients with no RH-PAT improvement after TAVI displayed a more severe AS and had lower blood pressure after TAVI. This might be due to a more disturbed blood flow in patients with a smaller aortic valve area and higher peak aortic valve velocity.The relationship between AS severity, endothelial dysfunction and TAVI has to be investigated in future research that apply longitudinal study designs.

The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.

Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.

Clinical and pathogenetic features of the development of endothelial dysfunction in patients with chronic kidney disease and its contribution to the development of cognitive impairments

THE AIM: to study the clinical and pathogenetic features of the development of endothelial dysfunction (ED) in patients with chronic kidney disease stages 3A-5D and its contribution to the development of cognitive impairment.PATIENTS AND METHODS: The study included 80 patients with CKD stages 3A-5D aged from 26 to 79 years (average age 58.9 ± 1.4 years): 43 women (average age 60.1 ± 1.9 years) and 37 men (average age 57.4±2.3 years). The patients were divided into 2 groups: group 1 included 40 patients with CKD 3A-5 (average age 59.9 ± 2.1 years), group 2 included 40 patients with CKD 5D (average age 58.1 ± 2 years). All patients underwent common and biochemical blood tests, the levels of endothelial nitric oxide synthase 3 (eNOS-3) and endothelin-1 (END-1) were determined, an endothelium-dependent vasodilation test (EDVD) was performed, testing for the presence and severity of cognitive disorders using the Montreal Cognitive Assessment Scale (MoCA) and the Mini Mental State Examination (MMSE).RESULTS: The prevalence of ED in the overall cohort of patients based on the results of a positive test with EDVD was 55 % of cases. ED was statistically significantly more often detected in the group of patients receiving hemodialysis treatment compared to patients in group 1: 70 % versus 40 %, respectively (p=0.007). The level of eNOS-3 in group 1 was higher compared to group 2 and amounted to 1.01±0.5 ng/ml versus 0.76±0.3 ng/ml (p=0.008). While the level of END-1 was statistically significantly lower in patients of group 1 compared to group 2 and amounted to 45.4±9.1 pg/ml versus 54.9±4.7 pg/ml (p<0.001). Cognitive impairments were identified in the general cohort: according to MMSE – in 67.5 % of cases, according to MoCA – in 71.3 %, and were more common in group 2. There were no statistically significant relationships between the results of the EDVD test and testing on the MoCA and MMSE scales. The level of eNOS-3 was lower in the subgroup of patients with cognitive impairment according to MoCA compared to the subgroup without it: 0.73±0.1 ng/ ml versus 0.94±0.2 ng/ml (p=0.127). The content of END-1 was statistically significantly higher in the subgroup of patients with cognitive impairment according to MoCA – 52.98±1.2 pg/ml compared to the subgroup without it – 47.67±1.5 pg/ml (p=0.043). When assessing the relationship between the levels of eNOS-3 and END-1 and the results of the EDVD test, it was found that in patients with a positive test in group 1, the level of eNOS-3 was statistically significantly higher compared to group 2 (p=0.01). An inverse relationship was observed for END-1; its level was lower in patients of group 1 compared to group 2 (p<0.01).CONCLUSION. Thus, the study revealed a high prevalence of endothelial dysfunction in patients with CKD stages 3A-5D. Progressive loss of renal function leads to dysregulation of the molecular mechanisms controlling vascular tone and the development of ED. eNOS-3 and END-1 have demonstrated high sensitivity for ED verification, and their detection improves the quality of the EDVD test. The development and progression of ED in patients with CKD is a multifactorial process that leads to hemodynamic disturbances in various organs and tissues, their damage and has a negative impact on the patient’s quality of life, his cognitive status and life expectancy.

Thrombomodulin as a promising Marker of Endothelial Dysfunction in Hemodialysis Patients with Non Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with endothelial dysfunction which is a common problem in haemodialysis patients and risk for high cardiovascular mortality in haemodialysis. Thrombomodulin is a promising marker of endothelial cell injury in different pathological conditions. This study evaluates the additive effect of non-alcoholic fatty liver disease (NAFLD) in prevalent HD (hemodialysis) patients on endothelial dysfunction. Methods This is a case-control study which was conducted on 60 ESRD (end-stage renal disease) patients on conventional hemodialysis and 30 apparently healthy controls. Patients were divided into 2 groups: group A (N = 30): with NAFLD& group B (N = 30): without NAFLD, excluding elderly, diabetic, chronic liver disease, advanced heart failure, active infection, COVID-19 infection and autoimmune disease& patients withhemodialysiscatheters. Thrombomodulin was measured for all participants by ELISA technique. Results Thrombomodulin had the ability to detect endothelial dysfunction in patients with NAFLD at Cut off value <0.8 ng/ml with sensitivity 53.33, specificity 80, PPV 72.7 and NPV 63.2. On comparing Thrombomodulin in patients with NAFLD(4.378±3.762 ng/ml), Non NAFLD (1.126±0.591 ng/ml)and control (0.755±0.314ng/ml) there was significant difference (P- value<0.001). Post hoc analysis showed significantly high Thrombomodulin level in patients with NAFLD compared to Non NAFLD and control with p-value<0.001 while there was no significant difference between patients with (Non NAFLD and control) p-value 0.792. NAFLD patients with higher Thrombomodulin level have 2.5 times higher risk to have endothelial dysfunction. There was no significant correlation between Thrombomodulin and all variables in the study. Conclusions Thrombomodulin can be used as specific marker for endothelial dysfunction in hemodialysis patients with Non Alcoholic fatty liver.

Changes of P-selectin level in endothelial dysfunction in patients with acute cardiovascular events and sepsis

Changes of P-selectin level in endothelial dysfunction in patients with acute cardiovascular events and sepsis

Effect of omega-3 fatty acid supplementation on markers of inflammation and endothelial function in patients with chronic heart disease: A systematic review and meta-analysis.

Chronic heart disease (CHD) is still a major global cause of morbidity and mortality, necessitating effective therapeutic interventions to mitigate its progression. Omega-3 fatty acids (FAs) have garnered attention for their potential anti-inflammatory and endothelial-protective properties in CHD management. The present study aims to assess the efficacy of Omega-3 FA supplementation on markers of inflammation and endothelial function in patients with CHD. To achieve this, we used the relevant keywords to search international databases (Web of Science, PubMed, Embase, and Scopus) and extract publications evaluating the effectiveness of omega-3 FA supplementation on inflammation markers and endothelial function in patients with CHD. STATA (version 15) and the random and fixed-effects models were used to evaluate the collected data. Thirteen clinical trial studies met inclusion criteria, with a total sample size of 853 individuals (406 cases and 447 controls). The cases had a mean age of 58 ± 10.3 years. The pooled results indicated that omega-3 Omega-3 FA supplementation significantly reduced the level of circulating IL-6 (SMD = -0.47, 95% CI -1.29 to 0.35, %, p < 0.001), hs-CRP (SMD = -0.21, 95% CI -0.70 to 0.28, p = 0.01), and TNF-α (SMD = -0.56, 95% CI -1.14 to 0.01, p < 0.001) in patients with CHD. Also, findings revealed that a daily supplement of omega-3 significantly increased FMD by 0.34% (95% CI: 0.14-0.54%, p < 0.001) as compared with placebo by a fixed-effect model in patients with CHD. These findings underscore the potential therapeutic utility of omega-3 fatty acid supplementation in modulating inflammation and endothelial dysfunction in patients with CHD.

Endothelial Dysfunction Linked to Ventricular Dysfunction in Children With Sickle Cell Disease, a 3D Speckle Tracking Study.

Sickle Cell Disease (SCD) is not a hematologic disease that occurs in isolation; it results in multi-organ complications. There is growing evidence of vascular stiffness as its underlying cause. This study aimed to investigate the relationship between endothelial stiffness and LV dysfunction in SCD patients and to explore its pathophysiology, particularly regarding the depletion of vasodilators such as Nitric Oxide (NO). 32 patients with established criteria for SCD and 40 healthy control subjects were selected for this case-control study. Comprehensive clinical assessment and assessment of endothelial function using Brachial Flow-mediated dilation (FMD) were performed, along with serum NO measurement, which was followed by diagnosis and echocardiographic assessment using 3D speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). Collected SCD cases showed echocardiographic features of Systo-diastolic dysfunction with reduced FMD compared to controls, denoting endothelial dysfunction in those patients. LDH showed a marked elevation, while serum NO showed a significant reduction in cases compared with controls. We also noted a positive correlation between FMD on the one hand and measures of ventricular dysfunction and level of serum NO on the other hand, the latter proving that reduction of NO is responsible for reduced endothelial function. We present the first report to date to outline the role of vascular stiffness as measured by brachial FMD in the induction of left ventricular dysfunction in SCD. We recommend that more research be conducted regarding possible strategies to replenish serum NO stores to delay microvascular injury and, in turn, ventricular dysfunction in SCD.

Correlation of intracardiac hemodynamics indicators with von Willebrand factor – Marker of endothelial dysfunction in patients with coronary artery disease combined with coronavirus disease (COVID-19)

Correlation of intracardiac hemodynamics indicators with von Willebrand factor – Marker of endothelial dysfunction in patients with coronary artery disease combined with coronavirus disease (COVID-19)

Endothelial Dysfunction in Heart Failure: What Is Its Role?

The endothelium is a continuous layer of cells that coats the interior walls of arteries, capillaries, and veins. It has an essential regulatory role in hemostatic function, vascular tone, inflammation, and platelet activity. Endothelial dysfunction is characterized by a shift to a proinflammatory and prothrombic state, and it could have a bidirectional relationship with heart failure (HF). Due to neurohormonal activation and shear stress, HFrEF may promote endothelial dysfunction, increase ROS synthesis, and reduce nitric oxide production. Different studies have also shown that endothelium function is damaged in HFpEF because of a systemic inflammatory state. Some clinical trials suggest that drugs that have an effect on endothelial dysfunction in patients with HF or cardiovascular disease may be a therapeutic option. The aim of this review is to highlight the pathogenetic correlation between endothelial dysfunction and heart failure and the related potential therapeutic options.

Features of coronary heart disease in a cohort of tajik patients and the condition of the vascular endothelium in its different clinical forms

Relevance. In the Republic of Tajikistan, in recent years there has been a steady increase in cardiovascular diseases. In this regard, special attention is paid to coronary heart disease with its various manifestations, which can often cause permanent disability, even death. In recent decades, there has been great interest among research scientists in studying the functioning of the endothelium in various forms of coronary heart disease, as well as in individuals with post-infarction cardiosclerosis as a complication of coronary heart disease. Despite the large number of studies in this area, the role and relationship of some sensitive markers of endothelial dysfunction with the clinical course of various forms of coronary heart disease have not yet been determined. That is why its detailed study is of unconditional clinical interest and provides the opportunity for a deep understanding of its theoretical aspects. Purpose of the study: to study risk factors for cardiovascular diseases and mark­ers of endothelial dysfunction in patients with stable angina pectoris in comparison with patients with post-infarction cardiosclerosis, i.e. previous myocardial infarction.Object and methods. Of 60 patients with various forms of coronary heart disease, whose average age was 62.6 ± 3.5 years, and 20 practically healthy individuals of the same age who made up the control group, three groups were formed: Group I (n = 20) included respondents without coronary heart disease; Group II (n = 30) included patients with stable angina pectoris of functional class II and III; Group III (n = 30) included patients who were diagnosed with post-infarction cardiosclerosis, i.e. previously suffered a myocardial infarction. Endothelial cell dysfunction was detected by determining desquamated endothelial cells, as well as by the activity of von Willebrand factor and the level of homocysteine in the blood plasma.Results. In the examined patients, risk factors for coronary heart disease in the form of arterial hypertension, physical inactivity and obesity were observed with greater frequency in persons with stable angina pectoris of functional class II, in contrast to those with functional class III. Patients with stable angina pectoris of functional class III all had chronic heart failure of varying severity (100%). Most patients had at least three risk factors for coronary heart disease. All persons with post-infarction cardiosclerosis had risk factors for coro­nary heart disease, while arterial hypertension was detected in 100%. Based on the indicators of endothelial dysfunction, it can be said that individuals in group III have a more severe functional and morphological condition (increased homocysteine levels, von Willebrand factor activity and the number of desquamated endothelial cells) compared to group II (p &lt; 0.001).Conclusion. In all forms of coronary heart disease (stable exertional angina of functional class II, III and post-infarction cardiosclerosis), the content of desquamated endothelial cells in the blood serum, the activity of von Willebrand factor and homocysteine are increased. A positive correlation was established between the level of desquamated endothelial cells and the level of homocysteine, von Willebrand factor, fibrinogen and platelets. After complex therapy of patients with various forms of coronary heart disease, the functional state of the endothelium improves (decrease in the level of desquamated endothelial cells, ho­mocysteine, von Willebrand factor).

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 &lt; 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).