Endothelial Dysfunction Formation Research Articles

CURRENT DATA ON THE ROLE OF HOMOCYSTEINE IN THE FORMATION OF CARDIOVASCULAR DISEASES

Recent research has made it possible to expand and complement the modern understanding of the regulation of many physiological processes of the body. At the same time, there are many controversial questions about the role of increasing homocysteine levels in the development of certain diseases, mainly cardiovascular pathology. Purpose. To analyze the current literature on the contribution of hyperhomocysteinemia to the formation of cardiovascular diseases (CVD). Material and methods. The data of foreign and domestic articles on the research topic found in Pubmed and eLibrary and published over the past 7 years are analyzed. Conclusions. Hyperhomocysteinemia leads to amplification of the adverse effects of classical CVD risk factors such as hypertension, smoking, lipid metabolism by participating in the formation of endothelial dysfunction.

Association of COVID-19 and Arterial Stiffness Assessed using Cardiovascular Index (CAVI).

COVID-19 is characterized by an acute inflammatory response with the formation of endothelial dysfunction and may affect arterial stiffness. Studies of cardio-ankle vascular index in COVID-19 patients with considered cardiovascular risk factors have not been conducted. The purpose of our study was to assess the association between cardio-ankle vascular index and COVID-19 in hospitalized patients adjusted for known cardiovascular risk factors. A cross-sectional study included 174 people hospitalized with a diagnosis of moderate COVID-19 and 94 people without COVID-19. Significant differences in the cardio-ankle vascular index values measured by VaSera VS - 1500N between the two groups were analyzed using parametric (Student's t-criterion) and nonparametric (Mann-Whitney) criteria. Independent association between COVID-19 and an increased cardio-ankle vascular index ≥ 9.0 adjusted for known cardiovascular risk factors was assessed by multivariate logistic regression. There were significantly higher values of the right cardio-ankle vascular index 8.10 [7.00;9.40] and the left cardio-ankle vascular index 8.10 [6.95;9.65] in patients undergoing inpatient treatment for COVID-19 than in the control group - 7.55 [6.60;8.60] and 7.60 [6.60;8.70], respectively. A multivariate logistic regression model adjusted for age, hypertension, plasma glucose level, glomerular filtration rate and diabetes mellitus showed a significant association between increased cardio-ankle vascular index and COVID-19 (OR 2.41 [CI 1.09;5.30]). Hospitalized patients with COVID-19 had significantly higher cardio-ankle vascular index values compared to the control group. An association between an increased cardio-ankle vascular index and COVID-19 was revealed, independent of age, hypertension, plasma glucose level, glomerular filtration rate and diabetes mellitus.

Endotoxic Septic Shock: Diagnosis and Treatment.

Endotoxin, also referred to as lipopolysaccharide (LPS), is a potent stimulator of the inflammatory cascade which may progress to sepsis and septic shock. The term endotoxic septic shock has been used for patients who have a clinical phenotype that is characterized by high endotoxin activity in addition to a high burden of organ failure; especially a pattern of organ failure including hepatic dysfunction, acute kidney injury, and various forms of endothelial dysfunction. Endotoxic septic shock has been a target for drug therapy for decades with no success. A likely barrier to their success was the inability to quantify endotoxin in the bloodstream. The Endotoxin Activity Assay (EAA) is positioned to change this landscape. In addition, medical devices using adsorptive technology in an extra-corporeal circulation has been shown to remove large quantities of endotoxin from the bloodstream. Focusing on the use of EAA to determine high concentrations of endotoxin will allow patients with endotoxic septic shock to be identified quickly and these patients may benefit most from removal of endotoxin using extracorporeal methods.

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

Влияние перенесенной преэклампсии на формирование сосудистых расстройств организма и органа зрения

The article presents the main pathogenetic mechanisms of endothelial dysfunction formation in complicated pregnancy and vascular pathology. The possible consequences of postponed preeclampsia are presented. The analysis of the literature suggests that preeclampsia should be considered as a pathology threatening an increased risk of the formation of vascular eye pathology, both in the short and in the long term after childbirth. Key words: preeclampsia, vascular retinal pathology, endothelial dysfunction

Reciprocal regulation of endothelial\u2013mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease

Endothelial–mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFβ1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.

Features of cognitive impairment in patients with chronic kidney disease stages 3A-5D: biological value of endothelial nitric oxide synthase.

THE AIM:a comprehensive assessment of the frequency, severity, and composition of cognitive impairments (CI) in patients with CKD stages 3A-5D, as well as to study the relationship between the levels of endothelial nitric oxide synthase (eNOS) and these impairments. PATIENTS AND METHODS:The study included 80 patients with CKD aged 26 to 79 years (mean age 58.9 ± 1.4 years), among them 43 women (mean age 60.1 ± 1.9 years) and 37 men (mean age 57.4 ± 2.3 years). All patients were divided into 2 groups: group 1 (pre-dialysis) included 40 patients (28 women and 12 men) with CKD 3A-5 (mean age 59.9 ± 2.1 years), group 2 (on dialysis) included 40 patients (18 women and 22 men) with CKD 5D (mean age 58.1 ± 2.1 years). Sarcopenia was verified according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP). The presence and severity of CI were determined using the short mental status assessment scale (MMSE) and the Montreal cognitive assessment test (MoCA). To identify endothelial dysfunction, all patients underwent a test with endothelium-dependent vasodilation of the brachial artery, as well as determination of the level of eNOS (ELISA Kit, USA) in serum. RESULTS:The prevalence of sarcopenia in the 1st group was 12.5 %, and in the 2nd group, 42.5 %. The average age of patients with sarcopenia was 66.1 ± 2.1 years. The prevalence of CI according to the MoCA scale in the general cohort was 70 %, while in the 1st group – 67.5 %, in the second – 72.5 %, in the subgroup with sarcopenia – 76.2 %. CIs, determined by the MMSE scale, were on average in 67.5 % of the surveyed, and the quantitative prevalence in the groups was identical, however, the qualitative composition of CIs in the comparative analysis differed in the severity of manifestations. In a comparative assessment of the prevalence of CI (according to the MMSE scale) in patients with sarcopenia, it was found that this indicator was significantly higher than in the subgroup without sarcopenia and amounted to 90.5 % and 59.3 %, respectively. In patients with sarcopenia, the level of eNOS was lower than the mean values compared with the general sample, patients of the 1st group and the subgroup without sarcopenia (0.75 ± 0.1 ng / ml, 0.88 ± 0.1 ng / ml, 1 ± 0.1 ng / ml and 0.92 ± 0.2 ng / ml, respectively (p = 0.02)). According to the results of the test with endothelium-dependent vasodilation, the prevalence of endothelial dysfunction in the total cohort of patients was 48.8 % (in the 1st group – 27.5 %, and in the 2nd group – 70 % (p = 0.001)), in the subgroup of patients with sarcopenia – 57.1 %. CONCLUSION:A high prevalence of CI was found in patients with CKD. The progression of CKD is associated with the formation of endothelial dysfunction and the development of CI. The latter significantly impairs the quality and life expectancy of patients. The main mechanism of their development is increasing endothelial dysfunction, and eNOS plays a key role in this process. Sarcopenia is associated with an increased risk of CI, regardless of the studied population and the criteria for the diagnosis of sarcopenia, and plays an important prognostic value.

Modern paradigm of treatment of hyperuricemia and gout in comorbid patients with the development of cardio-vascular pathology

The article presents the actuality of the problem of hyperuricemia (HU) and gout in modern medicine, caused by the high prevalence and socio-economic consequences associated with the development in patients with these pathologies of earlier and more severe course of atherosclerosis, coronary heart disease, chronic kidney disease (CKD) and increased mortality. Illustrated pathogenetic mechanisms of HU influence on the cardiovascular system, which are characterized by the formation of endothelial dysfunction, increased adhesion and aggregation of thrombocytes, blood rheology disorders, increased levels of inflammatory markers, renal function disorders. It is highlighted that in arterial hypertension (AH) a possible mechanism for increasing the concentration of uric acid (UA) is a violation of renal excretion due to reduced tubal secretion. The data of the studies are presented, showing that in patients with type 2 diabetes mellitus and higher UA concentration is associated with increased risk of fatal and non-fatal stroke. Modern recommendations of HU correction, approved in the Russian Federation, are highlighted, where the expediency ofcomorbid condition therapy, correction of diet and lifestyle are noted. The consensus of the European Society of Cardiology and the Russian Society of Cardiology (RSC) on the management of patients with HU with high cardiovascular risk (CVR) and the RSC Clinical Practice Guidelines for AH are presented. Based on these documents, all patients with AH are recommended to evaluate the level of UA in serum and consider it high - more than 360 pmol/l, it is recommended to perform urate-lowering therapy for patients with high CVR, with the target level below 300 pmol/l. Modern possibilities of pathogenetic therapy of gout are presented. It is noted that the use of febuxostat demonstrates not only higher efficiency in reducing and maintaining the level of UA, but also better tolerance, in comparison with allopurinol. It is emphasized that elderly people do not need to correct the dose of febuxostat, it can be used by patients with CKD.

Функциональная активность эндотелия и иммунный статус при атеросклеротическом поражении аорто-подвздошного сегмента и реваскуляризации

Objective. The aim of the study is the evaluation of endothelial functional activity and immune status in systemic and local blood flow in atherosclerotic lesions of the aorto-iliac segment after open and endovascular interventions and establishing the relationship with the lesion class. Materials and methods. The study included 190 patients with lesions of the aorto-iliac segment. Depending on the type of surgical intervention, patients were divided into two groups: group I (n=97) - patients who underwent aorto-femoral bypass surgery, group II (n=93) - patients who underwent TRANS-balloon angioplasty with stenting of the iliac arteries. Results. Violations of the functional state of the endothelium and the immune status in the systemic and local blood flow, which do not correlate with the TASC II lesion class (TransAtlantic Inter-Society Consensus II), were revealed. There were differences in the factors of endothelial damage (in patients of group II before surgery, the level of homocysteine in the systemic blood flow, oxidized low-density lipoproteins in the systemic and local blood flow), hemostatic form of endothelial dysfunction (in group I, inhibitor of tissue plasminogen activator type I (PAI-1) in the systemic and tissue plasminogen activator (t-PA) in the local blood flow) and apoptosis (higher in group I in the systemic and local blood flow). During revascularization of the aorto-iliac segment, there were violations of the hemostatic form of endothelial dysfunction in group II with an increase in PAI-1 by 14.8% (p<0.001) in the systemic blood flow and by 1.9 times (p<0.001) in the revascularized arterial segment compared to group I. In group II after revascularization was significantly higher the immunoglobulins (Ig) class A in system and the circulating immune complexes, interleukins 1 (IL-1) in local blood flow and lower levels of IgM, interleukins 6 (IL-6), IL-1 in system and IgA, IgM, IL-6 in local blood flow compared with I group. Conclusion. The study of the features of the functional state of the endothelium and the immune status will optimize the management strategies of patients after various types of revascularization interventions on the aorto-iliac segment.

Analysis of age and associated pathology in patients with hip artoprosthesics

Objective. To analyze the presence of concomitant pathology in patients of different age categories who underwent hip arthroplasty by different methods.
 Materials and methods. The study retrospectively analyzed 555 case histories of patients (282 men and 273 women) for the presence of concomitant pathology in different age groups (from 20 to 95 years). The age category was determined according to the 2015 World Health Organization age classification. Statistical processing was performed according to StatPlus programs, the differences were considered significant at p<0,05.
 Results and discussion. By age, patients were distributed as follows: juvenile (up to 25 years) – 2 patients (percentage of the total was 0,36 %); young (from 25 to 44 years) – 36 patients (6,49 %); middle-aged (from 45 to 59 years) – 132 patients (23,78 %); elderly (from 60 to 74 years) – 236 patients (42,52 %); senile (from 75 to 90 years) – 145 patients (26,13 %) and long-lived (over 90 years) – 4 patients (0,72 %). The average age of patients was 65.18±0.55 (M±m). Concomitant pathology was diagnosed in 484 patients (87,22 %). Depending on the existing concomitant pathology, patients were distributed as follows: no concomitant pathology – 71 patients (percentage of the total was 12,79 %); with hypertension – 38 patients (6.85 %); with diabetes – 11 patients (1.98 %); with coronary heart disease (CHD) – 104 patients (18,74 %); CHD + hypertension – 316 patients (56,94 %); with myocardial infarction – 3 patients (0,54 %); with a stroke – 2 patients (0,36 %); patients with encephalopathy of various genesis – 2 patients (0,36 %); with respiratory pathology – 3 patients (0,54 %); patients with systemic connective tissue diseases – 5 patients (0,90 %). Studies to date have shown a significant increase in comorbidities associated with the age of patients. One of the important predictors and unmodified risk factors for postoperative complications is the age of patients. The influence of age on the result of hip arthroplasty can be explained by a number of factors: the formation of endothelial dysfunction with impaired blood flow, changes in the blood coagulation system and more.
 Conclusions. With the development of medical practice, the average life expectancy of the population increases, the methods of arthroplasty and the anesthesiological support of operations are improved, the duration of surgical interventions is reduced. These factors contribute to the steady increase in the number of total joint arthroplasty, in the average age of patients undergoing arthroplasty and, accordingly, in the total comorbid load. That is why stratification of the degree of operative risk continues to be one of the most pressing problems in orthopedic patients.

Risk factors for the progression of chronic generalized periodontitis in women during menopause

Relevance. The global trend associated with increasing life expectancy leads to an augmentation of the frequency of diseases and conditions associated with the cessation of estrogen production. Hormonal changes in the female body, which lead to changes in the mineral density of bone tissue, microcirculation, and immune status, create prerequisites for the destruction of target organs, including periodontal tissues. The highest prevalence of periodontal pathology is observed against the background of estrogen deficiency, especially during menopause. The multifactorial nature of the Association of pathologies that develop against the background of estrogen deficiency requires further study. Purpose. Assessment of the contribution of various pathogenetic factors to the progression of oral pathology in women in the period of reproductive aging. Materials and methods . The paper uses the results obtained during the examination of 73 patients with chronic generalized periodontitis at various stages of menopause with an assessment of the level of reproductive hormones, endothelial dysfunction, major periodontogens, and local immunity. Results. An increase in the duration of menopause leads to the formation of endothelial dysfunction, increased destruction of periodontal bone tissue, and local immunosuppression. Conclusion. The progression of periodontal diseases in menopause depends on many factors, including estrogen deficiency, violations of local and general blood supply, immunity disorders and microbial flora.

Correction of systemic inflammation and endothelial dysfunction in patients with chronic obstructive pulmonary disease in combination with arterial hypertension under the influence of the therapy

One of the main pathogenetic mechanisms combining chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH) is a persistence systemic inflammation leading to the formation of endothelial dysfunction (ED), which serves as an independent predictor of the adverse prognosis of most cardiovascular diseases (CVD), while the treatment of patients with COPD in combination with AH requires the inclusion of drugs that have a beneficial effect on these pathological conditions. Prolonged-release indapamide has a number of pleiotropic effects, but most studies to study its effect on the state of endothelium and the intensity of systemic inflammation were conducted in patients with AH without associated bronchial obstructive diseases. The works carried out in conditions of comorbidity with COPD and according to the data of which the influence of diuretic drugs on the markers of systemic inflammation and ET in patients would be evaluated, were not found out, in this connection the present research was initiated and carried out. The aim of the study was to evaluate the dynamics of markers of systemic inflammation and ET in the inclusion of diuretics in the complex therapy of patients with COPD in combination with BA. Materials. Patients (n = 65: 50 men and 15 women) with stage I – IV COPD suffering from arterial hypertension (AH) I – III with initially elevated levels of systemic inflammation markers and ET, in whom the antihypertensive therapy performed was not effective enough, were included in the study. Results. The results of the research on estimation of dynamics of markers of system inflammation – highly sensitive C-reactive protein (hsСRP), an intercellular adhesion molecule of type 1 (sICAM-1) and ET – endothelin-1, sP-selectin at the inclusion of diuretics in the therapy of patients with COPD with AH are presented. When analyzing the dynamics of the studied markers, a decrease in their level was noted, but statistically significant changes were obtained only in patients against the background of prolonged-release indapamide treatment. Additional pleiotropic effects of indapamide, consisting in reduction of activity of markers of systemic inflammation and ET, are also shown. Its high efficiency in achieving and maintaining the target AH levels compared to hydrochlorothiazide has been demonstrated. Conclusion. The expediency of the inclusion of prolonged-release indapamide in the complex therapy of patients with COPD in combination with AH on the first line of antihypertensive therapy has been demonstrated due to its additional pleiotropic properties, which consist in the influence on the general pathogenetic links of the formation and progression of AH in COPD and its high antihypertensive efficiency in comparison with hydrochlorothiazide.

The relationship of endothelial dysfunction and metabolic manifestations of obesity

Introduction . Over the past three decades, the prevalence of overweight and obesity in the world has grown by almost 30–50% among adults and children. A number of metabolic and hemodynamic disorders, as well as the pathology of many organs and systems are often associated with obesity. The aim of our study was to compare the functional state of the endothelium in various variants of complicated obesity (СO). Materials and methods . The study included 66 people with СO whose average age was 47.3 ± 9.9 years, from this group 3 groups were formed depending on the complications of obesity (dyslipidemia, hypertension and impaired glucose tolerance). To assess the functional state of endothelium, we used the method of wavelet analysis of skin temperature fluctuations during cooling of the limb; endothelin-1 (ET-1), albuminuria (AC), and vascular endothelial growth factor (VEGF) were determined as markers of endothelial dysfunction. Results . The levels of VEGF, ET-1 and AC in the groups with СO did not differ significantly, however, they were significantly higher than in the comparison group. The results of the cold test revealed the absence of restoration of the amplitudes of fluctuations in skin temperature equally in all groups with CO compared with the control group (post-cold vasodilation indices (IPV) in group 1 – 0.45 (0.38–0.69, in group 2 – 0.59 (0.41–0.83), in group 3 – 0.66 (0.53–0.79), in the Control group – 0.91 (0.86–1.06), p<0.05). Correlations between biochemical and instrumental markers of endothelial dysfunction and insulin resistance indices were obtained: ET-1 correlated with insulin (r=0.49; p=0.02), HOMA index (r=0.55; p=0.01); AU value correlated with glycemia (r=0.70; p=0.02); The IVC vasoconstriction index correlated with the HOMA-IR index (r=0.62; p=0.05); The IPV-1 index decreased with increasing VEGF (r=–0.86; p=0.002) and HOMA-IR (r=–0.86; p=0.002). The IPV-2 index inversely correlated with the level of postprandial glycemia (r=–0.87; p=0.05), systolic blood pressure (r=–0.55; p=0.04), OT (r=–0.57; p=0.04) and ET-1 (r=–0.58; p=0.04). Conclusion . The unified basis of the revealed disorders in СO allows us to conclude that the factors of insulin resistance are complex: hyperglycemia, dyslipidemia, and arterial hypertension, which makes it difficult to identify the leading factor in the formation of endothelial dysfunction.

Ppathogenetic pathogenetic significance of subclinical inflammatory and apoptotic markers in elderly women with essential arterial hypertension

Introduction . The morphological and functional changes of the vascular wall endotheliocytes in case of essential arterial hypertension in elderly women are considered. They are due to the action of complex pathogenetic mechanisms of damage to the vascular wall, their dynamic changes with a chronic increase in blood pressure, against the background of endogenous inflammation and apoptosis, which have been little studied, which determines their relevance. The goal is to determine the importance of the processes of subclinical inflammation in the development and severity of endothelial injuries, apoptosis in hypertension in elderly patients. Materials and methods . The study involved 35 elderly women suffering from essential arterial hypertension of the II degree, II stage, who gave their consent to participate in the study. The degree of severity of endothelial dysfunction, which was established using dopplerography of the brachial artery by the linear method. The comparison group included 30 women with a normal level of blood pressure of a similar age without cardiovascular disease. The degree of dilatation of the brachial artery against the background of reactive hyperemia by more than 10% of the initial diameter was recognized as normal. The severity of subclinical inflammation was evaluated by the activity of TNF-α, HF CRP, the level of desquamated endotheliocytes, a blood test was performed using enzyme-linked immunosorbent assay (ELISA). Results . There was an increase in apoptotic activity (0.34±0.05 and 11.3±0.8), subclinical inflammation, and activation of proapoptotic receptors, which was 4 times higher (151.8±27.2 PG/ml) than in patients without this pathology (39.8±1.5 PG/ml). A strong direct correlation was found between the number of desquamated endothelial cellsendotheliocytemia and the degree of vasomotortonic dysfunction (r=0.62). In patients with arterial hypertension, the number of desquamated endothelial cells level of endotheliocytemia (1.91±0.05 cells/ml) is 1.5 times higher than in the comparison groupcontrols (1.1±0.02 cells/ml). Conclusion . With arterial hypertension in elderly patients, the formation of endothelial dysfunction has been established, its dynamic progression with increasing severity of tonic vasodilation disorders.

Disorders of endothelium-dependent vasodilation and oxidative stress markers in chronic kidney disease of the stage I

Introduction . The key point of cardiorenal relationships is the activation of the renin-angiotensin-aldosterone system and the formation of endothelial dysfunction. The aim of our study was to assess the state of endothelium-dependent vasodilation (EDVD) in patients with chronic kidney disease (CKD) as a function of the glomerular filtration rate (GFR). Materials and methods . It was investigated 40 healthy men (mean age 39.2±2.0 years) and 72 patients with CKD I st. (mean age 42.5±11.9 years). GFR was calculated using the formula CKDEPI. Tissue perfusion was studied by high-frequency ultrasound Doppler. Vascular reactivity of the skin was evaluated in functional tests with ionophoresis of acetylcholine. Results . Compared with healthy individuals, the increase in the volumetric blood flow velocity at the 2 minute test with acetylcholine was reduced only at a GFR value of 90–109 ml/min/1.73 m 2 , with large values of GFR, no indicator changes were detected. Also, only in these patients the most significant violations of oxidative status were noted in the form of an increase in the concentration of diene conjugates in the blood serum, a decrease in the concentration of tocopherol and general SH groups. Conclusions . Disturbance of endothelium-dependent vasodilation in the sample with acetylcholine in patients with the first stage of CKD was established with a GFR value of less than 109 ml/min/1.73 m 2 . Disturbance of the indicators of oxidative status was noted with a GFR value of less than 109 ml/min/1.73 m 2 .

Сосудистые осложнения глаза в отдаленные сроки после перенесенной преэклампсии

The article presents the main pathogenetic mechanisms of endothelial dysfunction formation in complicated pregnancy and vascular pathology. The possible consequences of postponed preeclampsia are described. The performed analysis of the literature allows to approve that preeclampsia should be considered as a pathology threatening an increased risk of the vascular eye pathology formation, both in the short and in the long-term periods after childbirth.

Markers of Endothelial Dysfunction: E-selectin, Endothelin-1 and von Willebrand Factor in Patients with Coronary Heart Disease, Including in Combination with Type 2 Diabetes Mellitus

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

EFFECT OF KALLISTATIN AND GHRELIN ON THE FORMATION OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC PANCREATITIS AND ATHEROSCLEROSIS

Introduction: The article is devoted to the optimization of complex diagnosis of endothelial dysfunction in patients with a combination of chronic pancreatitis and atherosclerosis. The aim: To study the level and effects of kallistatin and ghrelin on the formation of endothelial dysfunction in patients with chronic pancreatitis and atherosclerosis. Materials and methods: 54 patients with chronic pancreatitis were examined. The serum kallistatin level was determined by immunoassay using the Human Serpin A4 ELISA Kit from RayBiotech according to the application method. The serum ghrelin level was determined by immunoassay using the Human/Mouse/Rat Ghrelin Enzyme Immunoassay Kit from RayBiotech. Endothelial dysfunction was determined by the method proposed by D.Celermajer. Results: The study of endothelial-dependent and endothelial-independent vasodilatation is indicative of the presence of a pronounced ndothelial dysfunction in patients with chronic pancreatitis and atherosclerosis, which was manifested by a decrease in their level to 8.7±0.4% and 16.8±0.7%, respectively. The level of kallistatin and ghrelin in patients with chronic pancreatitis and atherosclerosis (15.44 ± 3.97 ng/ml and 276.69 ± 10.06 ng/ml respectively) also confirmed their important role in the formation of еndothelial dysfunction in these patients. Conclusions: The study of ghrelin and kallistatin level in serum can serve as a criterion for determining the severity of chronic pancreatitis and atherosclerosis, the development of endothelial dysfunction, and be a marker for predicting their future course.

Role ofpreconception endothelial dysfunction in development of obstetric complications

The article highlights the pathogenetic mechanisms of endothelial dysfunction formation and its role in the occurrence of gestational complications. The main tasks of the pregravid preparation of patients with diseases associated with endothelial dysfunction are considered. The relevance of early detection of risk factors for gestational complications caused by endothelial dysfunction is emphasized, and methods for its indirect assessment are described. A list of measures aimed at preventing the clinical implementation of endothelial dysfunction is given, and the possibilities of its therapeutic correction are described.

THE ROLE OF ENDOTHELIAL DYSFUNCTION AS A PART OF SYSTEMIC INFLAMMATORY RESPONSE IN PATHOGENESIS OF AGGRESSIVE AND INDOLENT NON-HODGKIN’S LYMPHOMAS

Objective. To study of manifestation of angiogenic and hemostatic forms of endothelial dysfunction and systemic inflammatory response in patients with non-Hodgkin’s lymphomas at the onset of disease. Material and methods. A total of 99 patients were enrolled in this study, including 55 patients with aggressive variants and 44 patients with indolent variants. The average age was 60.71±10.63 years. The serum level of vascular endothelial growth factor (VEGF) was measured as a marker of angiogenic form of endothelial dysfunction, the serum levels of thrombomodulin, D-dimers, soluble fibrin-monomer complex (SFMC) and level of Willebrand factor activity were used for evaluation of hemostatic form of endothelial dysfunction. To assess the degree of systemic inflammation response the serum levels of proinflammatory cytokines – TNF-α, IL-1β, IL-6 were measured, as well as serum level of acute phase proteins – C-reactive protein (CRP), fibrinogen. The serum level of IL-4 was used to evaluate antinflammation resistance. Results and discussion. Proinflammatory cytokine (TNF-α, IL-1β and IL-6) content was higher in both studied groups compare to the control group. Serum concentration of anti-inflammatory cytokine IL-4 in studied groups did not differ from the level in the controls group. CRP and fibrinogen serum content was increased only in group of patients with aggressive variants. There was a significant correlation between the level of CRP and proinflammatory cytokines in aggressive lymphoma group. Serum content of VEGF, thrombomodulin, D-dimers, SFMC and Willebrand factor activity were increased in both studied group in comparison with the control group. Concentration of thrombomodulin, D-dimers, SFMC and Willebrand factor activity was higher in patients with aggressive than in patients with indolent lymphomas. Conclusion. The signs of angiogenic and hemostatic forms of endothelial dysfunction in patients with aggressive and indolent variants of non-Hodgkin’s lymphoma were detected, as well as manifestation of systemic inflammatory response and attenuation of anti-inflammatory resistance with development of cytokines imbalance with proinflammatory cytokines predominance. The manifestations of systemic inflammatory response and hemostatic type of endothelial dysfunction with activation of coagulation were displayed more prominently in the aggressive lymphoma group.