Degree Of Endothelial Dysfunction Research Articles

The Positive Impact of Bariatric Surgery on Vascular Health.

Obesity is one of the most prevalent medical conditions in the Western world. There are many risk factors associated with obesity, including cardiovascular and pulmonary risk. Vascular health is not studied in obese patients, and whether obesity has an adverse effect on vascular health in these patients remains unknown. The first objective is to find a correlation between vascular health and obesity and whether obesity can be classified as a risk factor for vascular health. The second objective is to see if weight loss leads to an improvement in vascular health in patients. The study was conducted with pre- and post-surgical methods at Baylor Scott & White (BSWH) Medical Center, Temple, Texas, USA.Ten patients were approached, consented, and prepared to obtain baseline values through WatchPAT and EndoPAT devices prior to their bariatric surgery. Values obtained include their initial weight, respiratory disturbance index, apnea-hypopnea index, oxygen desaturation index, and degree of endothelial dysfunction via the EndoPAT device. Post-surgery, these values were obtained again and compared using Wilcoxon non-parametric analyses with a level of significance at p < 0.05. Our study results demonstrate a correlation between obesity and vascular health as endothelial dysfunction is widely seen. In our patients, after bariatric surgery, we saw a significant weight change (31.2% +11.2, p < 0.0001). There was a significant degree of endothelial function improvement after the weight loss (31.2% +34.7, p < 0.04). Our results indicate that there is a correlation between obesity and vascular health, which also correlates with cardiovascular risk. There is a significant reduction in endothelial dysfunction after weight loss. We believe that obesity is a risk factor for vascular health outcomes.

Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria.

Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)-treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2-162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4-27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (β = -2.83%, 95% CI, -4.44% to -1.21%, p = 0.001), estimated glomerular filtration rate (β = -0.04%, 95% CI, -0.07% to -0.01%, p = 0.004) and LDL cholesterol (β = -1.12%, 95% CI, -2.13% to -0.11%, p = 0.029). HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted.

Changes of endothelial function and oxidant status in insulin resistance and obesity under the conditions of iodine deficiency

Background. The topicality of the theme is due to the significant prevalence of cardiovascular diseases and an increase in costs for medical care, the high risk of disability, which characterizes the medical and social component of the problem. Pathological changes can be a manifestation not only of a cardiovascular disorder, but also develop as a result of other diseases, including diabetes mellitus, obesity, and thyroid pathology. One of the main mechanisms of morbidity and mortality is macrovascular complications that can occur in endothelial dysfunction and oxidative stress. The purpose of the research is to study the peculiarities of changes in the parameters of the endothelial system and oxidant status in animals with insulin resistance and obesity under conditions of adequate iodine supply and iodine deficiency. Materials and methods. Study included 75 sexually mature rats having received a high-carbohydrate, high-fat diet under conditions of adequate and limited iodine supply, followed by analysis of markers of carbohydrate metabolism, thyroid status, indices of endothelial function, lipid peroxidation and antioxidant protection. Results. The development of insulin resistance and obesity in a diet loaded with fructose and fats is accompanied by the development of endothelial dysfunction: in the blood serum, the level of endothelin-1 increases and inducible NO-synthase (iNO-synthase) is activated, in the myocardium, the activity of iNO-synthase increases compared to the data in animals who received a standard diet. The development of oxidative stress in experimental animals characterizes an increase in the content of diene conjugates and thiobarbituric acid-reactive substances in blood serum and myocardium against the background of inhibition of serum antioxidant enzymes (catalase, superoxide dismutase, ceruloplasmin, glutathione peroxidase, glutathione reductase). The degree of endothelial dysfunction and the intensity of lipoperoxidation increase with hypothyroid dysfunction against the background of iodine deficiency. Conclusions. Metabolic disorders under the conditions of insulin resistance and obesity are characterized by the development of endothelial dysfunction and oxidative stress, which are the predictors of the development of cardiovascular risks. Their intensity depends on carbohydrate and thyroid homeostasis.

The severity of endothelial dysfunction, oxidative stress, lipid metabolism disorders, decreased elastic properties and tone of peripheral vessels in patients with different POAG course variants, depending on the polymorphism of the genes of the biological clock

The purpose is to find out the relations of the vascular endothelium dysfunction, atherosclerotic damage to the vessels of the upper and lower limbs, the state of the antioxidant and prooxidant systems, and the lipid profile in patients with different POAG course — carriers of biological clock gene polymorphism.Materials and methods. 47 patients with advanced POAG underwent an examination that included visometry, biomicroscopy, ophthalmoscopy, perimetry, tonometry, thermometry, as well as determination of lipid metabolism, indicators of oxidative stress and antioxidant system. All patients were also tested for the degree of endothelial dysfunction by reactive hyperemia method, and the elastic properties and vascular wall tone by the volumetric sphygmomanometry method. POAG progression was determined by static automated perimetry and optical coherence tomography. The hospitalized patients were examined for daily melatonin profile and key biological clock genes typed by real-time polymerase chain reaction. The genetic material was taken by buccal scraping. Polymorphic variants were identified for CLOCK rs1801260 3111T/C and MTNR1B genes. 16 patients (S-POAG — 8, A-POAG — 8) were tested for melatonin taken from saliva samples at different times of the day in laboratory conditions with controlled nutrition and lighting using the DLMO protocol.Results. The predictors of glaucoma progression were found to be pronounced endothelial dysfunction and oxidative stress, which contribute to the acceleration of atherogenesis and a decrease in the elastic properties of the vascular wall of peripheral vessels. Clock 3111t-c circadian gene polymorphism was found to be interrelated with lipid metabolism disorders and increased lipid peroxidation in patients with POAG progression. Carriers of the G allele of the MTNR1B gene tend to have a higher level of triglyceride (TG) which grows in the evening hours if glaucoma is progressing. We showed that the phasal and amplitude characteristics of daily melatonin level, rather than its average level, may affect the state of the vascular wall of peripheral vessels in POAG patients.Conclusion. POAG progression is associated with pronounced oxidative stress, weakened antioxidant protection and dyslipoproteinemia. Differences in the lipid profile (dyslipidemia) and the indicators of oxidative stress and antioxidant protection in patients with stable and progressing glaucoma course are mutually related with Clock 3111t-c gene polymorphism (CG genotype).

Noninvasive Investigation of the Presence and Extent of Coronary Artery Disease by the Evaluation of Fingertip-Reactive Hyperemia

Objective: Fingertip-reactive hyperemia-peripheral artery tonometry (RH-PAT) is an emerging novel noninvasive method for evaluating endothelial function. We aimed to evaluate endothelial function with fingertip-reactive hyperemia by RH-PAT in symptomatic patients undergoing elective coronary angiography and to assess the relationship between the degree of endothelial dysfunction (ED) and the presence and the severity of coronary artery disease (CAD). Subjects and Methods: We assessed 92 patients. Before coronary angiography, endothelial function was measured by RH-PAT and reactive hyperemia index (RHI) was obtained. For each patient, the Gensini score was calculated according to the coronary angiographic findings to evaluate the severity of CAD. Results: In CAD (+) group, RHI (1.35 ± 0.57 vs. 1.74 ± 0.46, p = 0.001) mean values were lower than CAD (−) group. In multivariate logistic regression analysis, age, high-density lipoprotein, and RHI were found to be independent parameters predicting the presence of CAD. In multivariate linear regression analysis, RHI was found to be an independent predictor associated with the severity of CAD. In receiver operating characteristic curve analysis, RHI achieved an area under the curve of 0.763 (95% confidence interval 0.663–0.846, p = 0.001) for the ability to predict the presence of CAD. A cut-off value of 1.49 for an RHI predicted the presence of CAD with a sensitivity of 75% and a specificity of 72.9%. Conclusion: RH-PAT is an objective and highly reproducible test with superior diagnostic accuracy for the evaluation of ED. We found significant correlations between ED and the presence and the severity of CAD.

63 Peripheral endothelial function in patients affected by pulmonary hypertension. Relationship between endothelial function, haemodynamic parameters, and therapy response

Abstract Aims Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) of 25 mmHg or greater at rest, confirmed by right heart catheterization (RHC). The World Health Organization has classified PH into five clinical subgroups. Pulmonary arterial hypertension (PAH) (group 1) is characterized by loss and obstructive remodelling of the pulmonary vascular bed. These patients are characterized haemodynamically by the presence of precapillary PH, defined as an mPAP of 25 mm Hg or greater, pulmonary artery wedge pressure (PAWP) of 15 mm Hg or less, and pulmonary vascular resistance (PVR) of three Wood units (WU) or greater. Pulmonary hypertension due to left-sided heart disease (LHD) (PH-LHD) (group 2) occurs in HF. Patients with PH-LHD usually have isolated postcapillary PH (PAWP &amp;gt;15 mm Hg and PVR &amp;lt;3 WU), although some of them have combined postcapillary and precapillary PH (PAWP &amp;gt;15 mm Hg and PVR ≥3 WU). PH due to chronic lung disease (CLD) (PH-CLD) and/or hypoxia (group 3) can occur in many lung diseases. These patients have precapillary PH. Chronic thromboembolic PH (CTEPH) (group 4) is characterized by obstruction of the pulmonary vasculature by organized thromboembolic material and vascular remodelling, resulting from prior pulmonary embolism. Patients with unclear and/or multifactorial mechanisms are listed as group 5. Specific pulmonary vasodilators are approved only in PAH patients. While research was predominantly focused on pulmonary vasculature, little is known about the peripheral endothelial damage in different vascular beds in PH patients. To evaluate the relationship between the peripheral endothelial function and the haemodynamic parameters, in order to provide a non-invasive method for the indirect evaluation of mean pulmonary pressure and vascular resistance, to predict if the PH is a precapillary or postcapillary, to select more accurately the patients who should undergo RHC. Moreover, we investigate if there is a possible correlation between endothelial dysfunction and response to specific PH therapies. Methods and results Patients with suspected PH, based on symptoms, medical history, and clinics will undergo physical examination, ECG, echocardiography, and RHC. In all patients, endothelial function was assessed by FMD. Medical history, heart rate, systolic blood pressure, body mass index, WHO functional class, and medications were recorded. All patients underwent blood analysis, erythrocyte sedimentation rate (ERS), high sensitivity C-reactive protein (CRP), and NT-proBNP levels were assayed. Increased peripheral endothelial dysfunction in patients with precapillary PH, with a linear correlation between endothelium dysfunction and increased PVR at the right catheterization. To differentiate pre and post capillary PH forms by cut-off values of the FMD. The degree of endothelial dysfunction could be a marker of therapy response. Sequential combination therapy in the pre-capillary PH forms could be the one with a worst endothelial response than up-front combination therapy.

СОСТОЯНИИ СИСТЕМЫ СИНТЕЗА ОКСИДА АЗОТА ПРИ КОМОРБИДНОМ ТЕЧЕНИЕ БРОНХИАЛЬНОЙ АСТМЫ И ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНИ

Comorbidity is a common condition in medical practice. The presence of comorbid conditions in a patient makes a great contribution to the course and prognosis of the underlying disease, as well as the development of complications [12]. At the same time, diseases occurring with broncho-obstructive syndrome and arterial hypertension syndrome are widespread throughout the world [13, 14]. The aim of this study was to assess the degree of endothelial dysfunction associated with impaired nitric oxide synthesis, based on the state of the NO/NOS/ADMA system and genetic polymorphisms of the nitric oxide synthetase gene in patients with bronchial asthma combined with essential hypertension. Materials and methods Three groups of patients, 96 people each, were formed, corresponding in age and gender structure with a diagnosis of bronchial asthma (BA group), essential hypertension (EH group) and their joint course (BA+EH group). Serum concentrations of asymmetric dimethylarginine, symmetric dimethylarginine, genetic polymorphisms of nitric oxide synthase (synthases NOS3 786T/C and NOS3 894G/T) were determined. To determine the role of other factors in increasing the concentration of ADMA and SDMA, multiple linear regression analysis was performed. Results: according to the results of the study, for a group of patients with a combination of bronchial asthma and hypertension, there are increased levels of ADMA and SDMA, the T allele NOS3 786C/T is more common in hypertension, in multiple linear regression significant factors in increasing ADMA are the presence of hypertension, bronchial asthma, body mass index and glomerular filtration rate, for SDMA - the presence of hypertension, asthma and glomerular filtration rate. Conclusions: The comorbidity of bronchial asthma and arterial hypertension is associated with an increased serum concentration of ADMA and SDMA. The presence of the TT genotype of the NOS3 786C/T polymorphism is associated with an increased incidence of arterial hypertension in patients with asthma.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction

BackgroundSome studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age.AimsThe aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices.MethodsWe enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection.Results63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance.DiscussionPatients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

IN MILD HYPERTENSIVE PATIENTS 24-HOUR AVERAGE HEART RATE IS ASSOCIATED WITH EARLY CARDIAC DAMAGE AND ENDOTHELIAL DYSFUNCTION

Objective: To investigate the correlation of 24-hour average heart rate (HR) in untreated and recently diagnosed mild hypertensives, and evaluate their association with subclinical initial signs of cardiac target organ damage (TOD), and endothelial dysfunction. Design and method: A total of 400 outpatients with initial diagnosis of mild hypertension were recruited between December 2017 and November 2019. Ambulatory electrocardiogram and blood pressure (BP) were monitored in all patients. According to the 24-hour average HR, patients were divided into fast HR group (24-hour average HR &gt; 75 beats/minute, n = 220) and non-fast HR group (24-hour average HR less or equal to 75 beats/minute, n = 180) We evaluate endothelial dysfunction by flow mediated vasodilatation (FMD) at the level of brachial artery. We use echocardiography to determine the presence of initial signs of (TOD), (presence of signs of left ventricular hypertrophy left ventricular mass indexed for height (LVMi) &gt; 48 g/m2 for men and &gt; 44 g/m2 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) &gt; 34 ml/m2). Results: Endothelial dysfunction, LVMi and LAVi, 24-hour average HR, night and day average HR, diastolic BP, and daytime systolic BP were higher, while nocturnal BP drop rate was lower in patients with fast HR group than those in non-fast HR group (all P &lt; 0.04). Twenty-four-hour HR, the degree of endothelial dysfunction and TOD increased significantly with increases of office BP (P &lt; 0.04). The 24-hour average HR and resting HR were correlated positively with the presence of TOD (r = 0.159, 0.262, respectively, both P &lt; 0.01), and degree of endothelial dysfunction (r = 0.155, 0.260, respectively, both P &lt; 0.01). Multivariate linear regression analysis showed that the level of BP (B = 17.420, 16.540), nocturnal BP drop rate (B = 1.652, 1,586), and 24-hour average HR (B = 0.558, 0.5442) were correlated with the presence of TOD and FMD cuantified endothelial dysfunction. Conclusions: In patients with initial diagnosis of mild hypertension, 24-hour average heart rate is associated with the early cardiac damage and endothelial dysfunction, confirming the participation of increased heart rate in initial cardiac and vascular changes in human hypertension.

Mildly elevated thyroid-stimulating hormone is associated with endothelial dysfunction and severe preeclampsia among pregnant women with insufficient iodine intake in Eastern Cape province, South Africa

Background Preeclampsia and hypothyroidism are associated with endothelial dysfunction. Iodine deficiency is a risk factor for subclinical hypothyroidism in pregnancy. However, there is a paucity of data on the relationship between iodine nutrition state in pregnancy, the degree of endothelial dysfunction, and the risk of preeclampsia. Methods Ninety-five normotensive pregnant women, 50 women with preeclampsia with no severe features, and 50 women with severe preeclampsia were enrolled into the current study from the maternity units of Nelson Mandela Academic Hospital and Mthatha Regional Hospitals in Eastern Cape Province, South Africa. Urinary iodine concentration (UIC), serum markers of thyroid function, aortic augmentation index, and pulse wave velocity (PWV) were compared. Results Median UIC was 167.5, 127.7, and 88.5 µg/L, respectively for normotensive pregnant women, those with preeclampsia and severe preeclampsia (p = .150). Participants with severe preeclampsia had significantly higher median thyroid-stimulating hormone (TSH) and oxidized LDL than normotensive and preeclamptic women without severe features (respectively 3.0, 2.3, and 2.3 IU/L; 1.2, 1.0, and 1.0 IU/L, p < .05). The median Aortic augmentation index was 7.5, 19.0, and 21.0 (p < .001), and the pulse wave velocity 5.1, 5.7, and 6.3, respectively for normotensive, preeclampsia, and severe preeclampsia participants (both p < .001). In linear regressions, TSH, age, and hypertensive disease were independent predictors of elevated PWV. Conclusion Upper normal-range TSH levels in women with severe preeclampsia were associated with markers of endothelial dysfunction. The low UIC and trend towards the elevation of thyroglobulin suggest that inadequate iodine intake may have increased TSH levels and indirectly caused endothelial dysfunction.

Vascular, molecular and cellular mechanisms of development of cognitive impairments after occlusion of carotid arteries

The study was aimed at determining the role of vascular endothelial dysfunction in induction of molecular and cellular mechanisms of the development of cognitive impairments after occlusion of common carotid arteries. The experiments were carried out on Wistar rats. The animals were divided into 2 groups: group 1 - control, sham-operated animals; group 2 - rats with cerebral ischaemia-reperfusion. The model of cerebral ischaemia-reperfusion was reproduced by means of simultaneous occlusion of common carotid arteries (for 5 minutes). The degree of endothelial dysfunction was assessed by determining the amount of circulating endotheliocytes and concentration of nitrogen oxide products in blood plasma. In the brain, we measured the content of malonic dialdehyde, the activity of superoxide dismutase and catalase. Pathomorphological studies of cerebral structures and morphometric analysis of the number of damaged neurons in ischaemic exposure were carried out by means of light microscopy. Cognitive functions in rats were assessed by means of conditioned reaction of passive avoidance and the test of pattern identification. Common carotid arteries occlusion in rats induced an increase in the level of circulating endotheliocytes and a decrease in end products of nitrogen oxide - nitrites in blood plasma as compared with the control (p≤0.05); the content of malonic dialdehyde in the brain increased 2.6-fold, the activity of superoxide dismutase and catalase decreased 5.9-fold and 2.8-fold, respectively (p≤0.05). The findings of pathomorphological examination registered signs of vasoconstrictive reactions, endothelial oedema, an increase in the proportion of damaged neurons in the cortex of greater hemispheres and hippocampus (p≤0.05). It was determined that occlusion of common carotid arteries in rats resulted in memory disorders revealed in tests of conditioned passive avoidance response and pattern identification (p≤0.05). Occlusion of common carotid arteries in rats becomes a cause of endothelial dysfunction, neurometabolic alterations, damage of neurons in vulnerable regions of the cerebral cortex, hippocampus and cognitive impairments. Damaging factors of the neurovascular system are intensification of oxidative processes and a decrease in the level of antioxidant defence, presenting important targets of neuroprotection.

Structural and functional changes of abdominal organs in patients with hepatocerebral degeneration

The paper presents the results of ultrasound diagnostic of 76 patients with neurological forms of hepatocerebral degeneration (HCD) or Wilson’s disease (WD), who were examined and treated at the clinic of the Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine. According to ultrasound diagnostic, all patients had pathological changes in the liver. In 58% of patients these changes corresponded to chronic hepatitis, in 42% - liver cirrhosis, and in 32% of patients were reported for portal hypertension. Background hepatic hemodynamics of patients was within normal limits, but in 82% of them the reaction to food load was negative. Doppler study showed that background hepatic hemodynamics in patients with neurological forms of hepatocerebral degeneration (GCD) was within normal limits. However, the food load showed that 82% of patients had impaired reciprocal autoregulation of liver microcirculation. This indicates a decrease in their compensatory-adaptive capacity of the liver. This position is confirmed by the fact that 70% of these patients have a decrease in vasoactive endothelial function. Our study of the functional state of the vascular endothelium showed that patients with GCD have a significant decrease in vasoactive endothelial function. In general, the group was only 8.12% at a rate of 10% or more. Despite the young average age of our patients (29.7 years), only 30% of patients had a normal vasoactive reaction. These were patients under the age of 25 from the group of chronic hepatitis. The degree of endothelial dysfunction was significantly higher in patients with liver cirrhosis compared with chronic hepatitis. According to ultrasound elastography, in the vast majority of examined patients with GCD (88%) there was increased stiffness of the liver parenchyma. On the average on group of patients it made 10,62 KPA with a range from 4,74 to 20,69 KPA (norm 0,4-6,0 KPA). Thus, patients with neurological forms of GCD, which are observed by a neurologist, it is necessary before each course of treatment, but at least 1-2 times a year, to conduct ultrasound of the abdominal cavity.

Аntioxidant Status and Lipid Metabolism in Patients with Different Forms of Primary Open-Angle Glaucoma Progression

Purpose: to study the antioxidant system and lipid status of serum and evaluate the effect of Cytoflavin on these characteristics in patients with progressive and stable primary open angle glaucoma (POAG).Patients and methods. 67 patients with advanced stage POAG were observed. The average age was 66.3 ± 1.5 years. According to the course of the glaucoma process all patients were randomized into 2 groups: the 1st group with the stable glaucoma (31 patients) and the 2nd group with rapidly progressive glaucoma (36 patients). The progression criteria of POAG were global ganglion cell loss volume (GLV) and perimetric index (mean deviation-MD). For assessment of the reactivity of the vascular endothelium, a test with reactive hyperemia was performed using ultrasound method. The assessment of oxidative stress (OS) including peroxides, malonyldialdehyde (MDA) and the total antioxidant capacity of serum (AOS) were evaluated. The investigations of lipid metabolism included the level of cholesterol total (CT), cholesterol of low-density lipoproteins cholesterol (LDL-C), high-density lipoproteins cholesterol (HDL-C), triglycerides (TG) and atherogenic index (AI).Results. In the 2nd group there was the significant decrease of the mean GLV indices compared to those in the 1st group (7.16 ± 2.5 и 1.06 ± 0.2, respectively, р &lt; 0.001). The mild degree of endothelial dysfunction (ED) predominantly was detected in patients of the 1st group (69 % of cases). The moderate and marked ED were found in patients with progressive POAG (68 and 25 %, respectively). The high level of OS in serum was determined in 43 % of patients of the 1st group and in 69 % of patients of the 2nd group (significant increase of peroxides and MDA). In patients with progressive POAG the mean indices of lipid metabolism (CT, LDL-C, HDL-C, TG, AI) were significantly higher than in healthy subjects (р &lt; 0.001). Cytoflavin had a positive effect on the vascular endothelium function, normalization of lipid metabolism and decrease of OS in serum with increasing AOS in patients with progressive POAG.Conclusion. The assessment of the indices of OS, AOS and lipid metabolism enable us to determine the risk of progression of POAG and evaluate of the effectiveness of treatment.

Markers of Endothelial Injury and Dysfunction in Early- and Late-Onset Preeclampsia.

With regard to differences in the clinical symptoms of preeclampsia (PE), the degree of endothelial dysfunction may differ between early and late-onset preeclampsia (EOP and LOP). The authors of this study examined it by assessing the endothelial injury level in women with EOP (20 patients) and LOP (20 patients) and in normotensive pregnant women (20 patients) in their late second and third trimesters of pregnancy, using the two markers—the serum concentration of hyaluronan (HA) and the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1). The serum concentrations of HA and sVCAM-1 did not differ significantly between the EOP and LOP patients. However, these were statistically higher than that of the control group participants (p < 0.05; p < 0.001). A significant correlation between the levels of HA and sVCAM-1 was found both in the entire group of patients with preeclampsia (p = 0.0277) and in women with late-onset disease (p = 0.0364), but not in the patients with early-onset preeclampsia (p = 0.331). The obtained results indicated a comparable level of endothelial injury in the two types of PE. The presence of a similar degree of endothelial injury in patients with EOP and LOP should create awareness among all clinicians about the possible fatal complications in both groups of patients with PE.

Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition.

We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. Methods and Results: L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (p ≤ 0.01), and was higher in SI than in PFO or OS patients (p ≤ 0.05, p ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (p ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (p ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p ≤ 0.0001, p ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. Conclusions: A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy.

The role of the endothelium in selected diseases of the cardiovascular system

In recent years, the role of endothelial function assessment in the recognition of preclinical forms of cardiovascular disease has increased. At the same time, there are tools to assess endothelial function that are fully objective and automated, which significantly affects the ease of assessment. It seems that they can displace the most commonly used method of measuring endothelial function, which is dilatation of the artery in response to ischemia. In addition to the diagnostic value, the improvement of endothelial function may be the goal of treatment of patients with known cardiovascular diseases. The beneficial effect of physical activity in patients after ST segment elevation myocardial infarction on endothelial function has been demonstrated. Patients with more severe, baseline endothelial diffusion experienced the greatest benefits. Similarly, a positive effect of beta-blockers on endothelial function has been demonstrated. Other antihypertensive drugs also have this effect. Endothelial dysfunction also affects the occurrence of arrhythmias, including atrial fibrillation. However, it has been shown that the longer duration of the arrhythmia episode decreases the degree of endothelial dysfunction as assessed by measuring serum biomarkers’ levels. The situation may be related to the adaptation of the body to the occurrence of arrhythmias.

C-type natriuretic peptide plasma levels and whole blood mRNA expression show different trends in adolescents with different degree of endothelial dysfunction

C-type natriuretic peptide (CNP) is an endogenous adipogenesis regulator whose plasma levels in childhood are known, while no data are available on its expression. Our aim was to evaluate both CNP plasma levels and CNP system expression in whole blood obtained from normal-weight (N, n = 24) and obese (O, n = 16) adolescents (age:13.5 ± 0.4 years). Endothelial function was assessed measuring reactive hyperemia index (RHI). CNP plasma levels, evaluated with specific RIA, resulted significantly lower in O than in N (6.1 ± 0.8 vs.15.2 ± 1.3 pg/mL; p < 0.0001), while CNP/NPR-B/NPR-C mRNA, measured by Real-Time PCR, resulted similar in N (4.1 ± 1.7; 5.0 ± 1.6; 2.2 ± 0.9) and in O (4.3 ± 1.6; 3.5 ± 1.1; 2.3 ± 0.8). RHI was significantly lower in O than in N (1.4 ± 0.08 vs.2.1 ± 0.04, p < 0.0001). Dividing all subjects according to the RHI median value, irrespective of the presence or absence of obesity (Group 1 > 1.9, n = 23, Group 2 < 1.9, n = 17), CNP plasma concentrations resulted significantly (p = 0.014) higher in Group 1 (14.6 ± 1.6) than in Group 2 (7.5 ± 1.0), showing a significant correlation with RHI (p = 0.0026), while CNP mRNA expression was, surprisingly, higher in Group 2 (7.0 ± 2.3) than in Group 1 (1.8 ± 0.4; p = 0.02). NPR-B mRNA resulted similar in both Groups (4.3 ± 1.6; 4.7 ± 1.3) and NPR-C significantly higher in Group 2 (p = 0.02). Our data suggest different trends between CNP plasma levels and expression, assessed for the first time in whole blood, that could reflect changes occurring both at CNP transcriptional level in activated leukocytes due to inflammation, and at circulating levels, due to CNP paracrine/autocrine activities. This could represent an interesting area for new therapies able to modulate endothelial dysfunction.

Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma

Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma. We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1. Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function. Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1). We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.

MEDIATORS OF ENDOTHELIAL DYSFUNCTION IN CEREBRAL ISCHEMIA IN PREMATURE INFANTS

N preterm infants with cerebral ischemia, the blood level of such mediators of endothelial dysfunction (MED), as endothelin-1, nitric oxide, angiotensin II, homocysteine, neurotrophic factors, tissue type plasminogen activator and von Willebrand factor was quantified. The established patterns of changes in the blood level of these mediators, depending on the degree of prematurity and severity of cerebral ischemia, reflect the severity of impairment of the functional state of the endothelial system. The quantitative data on the blood MED level in premature infants can be considered as criteria for the assessment of the degree of endothelial dysfunction, as in choosing modes for adequate timely correction of cerebrovascular disorders in newborns.

Relationship between endothelial dysfunction and development of complications of metabolic syndrome

The article presents the analysis of literature data on the pathogenetic role of endothelial dysfunction (ED) in the development of complications of metabolic syndrome (MS). There are two main signs of MS development - abdominal obesity (AO) and primary insulin resistance (IR). IR and concomitant hyperinsulinemia have both direct and indirect atherogenic effects on vascular walls, lead to the development of dyslipidemia, a number of hormonal and metabolic disorders, activation of the sympathoadrenal system, ie, are the basis of almost all components of MS. Despite the high margin of safety of the circulatory system, there comes a time when, due to frequent vasoconstrictor effects thickening of the walls of resistive vessels occurs to limit local perfusion. The thickening of the walls of arteries develops, that is, the modeling of the vascular wall occurs, leading to an increase of the total peripheral vascular resistance with normal tone of smooth muscles. Currently, the concept of ED is formulated as a key link of insulin resistance and atherogenesis in MS. Methods for studying endothelial function have been created and are introduced into clinical practice. New approaches to directed correction of endothelial dysfunction are being developed. Prospective studies have shown that the degree of endothelial dysfunction may be important in predicting cardiovascular events in patients with or without identified vascular disease. Probably, ED may also be related to the pathogenesis of diabetes mellitus type 2 (DM2). Since all components of MS can have an adverse effect on endothelium, ED can be an extremely common phenomenon in patients with metabolic syndrome and can act as a predictor of increased risk of cardiovascular diseases and DM2 in this population.