The paper summarizes data about the structure and function of the endothelium of the brain vessels, heart, lungs, liver and kidneys. Endothelial cells have important functions, the implementation of which depends on the hemodynamic and cellular microenvironment of a particular organ or tissue. The manifestations of endothelial dysfunction, changes in the direction and intensity of the formation of individual endothelial factors due to the heterogeneity of the endothelium, and depend on the structure, organization and biochemical functions of the authority. Understanding the differences in morphology, ultrastructure, gene expression and function of various subpopulations of endothelial cells may be of therapeutic relevance for regenerative medicine, cell therapy of endothelial dysfunctions and ischemic revascularization.

Objective. To elucidate the association between polymorphic markers of the genes of C-reactive protein (CRP), interleukin 10 (IL10), interleukin 6 (IL6), lymphotoxin alpha (LTA) and tumor necrosis factor (TNFA) and changes of arterial stiffness in hypertensive patients. Design and methods. The study included 130 patients with hypertension (HTN) (64 (49,3%) men and 66 (50,7%) women), average age 63,7 ± 12,87 years. The intima-media thickness was measured by the method proposed by P. Pignolli. The arterial stiffness was assessed by the carotidfemoral and carotid-radial pulse wave velocity (PWV). Central aortic pulse pressure (PP) was calculated using pulse contour analysis. Results. An association of polymorphic markers of A (-3872)G, G (-2667)C, A (-5237) G CRP gene, G (-1082)A gene IL10, C (-174)G gene IL6, and A (-308)G gene TNFA with pulse wave velocity, PP in the aorta, the presence of atherosclerotic plaques of carotid arteries was found. Among patients with aortic PP > 50 mmHg the frequency of AA genotype carriers of polymorphic marker C804A LTA gene was higher (p = 0,037). Carriers AA genotype had a significantly greater carotid-femoral PWV as compared with native CC genotype (13,4 and 11,9 m/s, p = 0,042) and higher PP in the aorta. Also, higher PP and aortic PWV were found in carriers of GG genotype of A (252)G LTA gene. Among patients with the presence of atherosclerotic plaques of carotid arteries the frequency of AA genotype of the G (-3014)A CRP gene was higher (p = 0,031). Conclusion. Thus, we have shown that CRP gene polymorphism is associated with the development of carotid atherosclerosis and increased central PP, while lymphotoxin alpha gene polymorphism is associated with the increase in arterial stiffness in high risk hypertensive patients. Our data confirm the involvement of pro-inflammatory cytokines in the development of atherosclerosis and endothelial dysfunction.

Objective. To determine the pathogenic conjugation of functional disorders of the endothelium with the severity of myocardial dysfunction and heart failure in hypertensive elderly patients. Design and methods. The study included 66 patients with hypertension (HTN) II and III stages of 60–74 years (mean age — 66,1 ± 0,5 years), and 26 age-matched people without heart disease. The following examination were performed: brachial artery dopplerography, echocardiography with doppler analysis of transmitral diastolic flow, evaluation of laboratory markers of subclinical inflammation, dyslipidemia, oxidative and nitrosative stress, tolerance to physical activity. Results. Mild and moderate severity of endothelial dysfunction (ED) in elderly HTN patients correlaes with diastolic myocardial disorders, confirmed in 70% patients. Severe endothelial lesions in 18% patients correspond to systolic myocardial dysfunction due to concentric myocardial remodeling, identified in 87,5%. The ED progression is characterized by activation of oxidative and nitrosative stress and loss of the antioxidant defense mechanisms, which accelerate death and desquamation of endothelial cells. Conclusions. Involutive reduction of the vascular endothelium functional properties is accompanied by the development of favorable cardiac remodeling and mild diastolic dysfunction. The progression of endothelial lesions in HTN is associated with the severity of myocardial dysfunction: mild or moderate endothelial functional disorders predominantly are associated with isolated diastolic disorders with prevalence of concentric left ventricular hypertrophy and heart failure NYHA II. Higher degree of ED is associated with systolic left ventricular dysfunction and higher functional class of chronic heart failure due to the concentric left ventricular remodeling.

Background. Absence of nocturnal decrease (non-dipper) or an extreme decrease of blood pressure (BP) (overdipper) may be a sign of vascular dysregulation. Non-dipper pattern is associated with increased risk of strokes and cardiovascular events. Over-dipper pattern increases the risk of non-arteritic anterior ischemic neuropathy and glaucoma progression. Daily BP profile in young and middle-aged adults with retinal vein occlusion (RVO) has not been previously examined. The target organ damage is determined by BP dynamics, regional microcirculation and associated perfusion pressure decrease, which verifies the relevance of our study. Objective. To evaluate the diurnal BP variation, the prevalence of arterial hypertension (HTN) and its character, ocular blood flow in RVO in young and middle-aged adults. Design and methods. The study included 30 patients with RVO. In all patients, routine ophthalmic examination was performed, as well as an additional ocular blood flow assessment (ophthalmoplethysmography, ophthalmorheography, ophthalmosphygmography, and fluorescein angiography). 24‑hour blood pressure monitoring (BPM) was performed to estimate systemic hemodynamics. Results. Statistically significant differences between eyes were noted in visual acuity (p = 0,001) and retinal thickness in macular area (p < 0,001). Patients with HTN showed lower visual acuity (р = 0,04), ocular blood flow parameters (p < 0,05) and retinal mean sensitivity (RMS) (р = 0,02) according to automated static perimetry. Fluorescein angiography showed zones of peripheral retinal ischemia with a mean area of 103 mm² (from 0 to 250 mm² ). 8 patients had masked HTN according to ambulatory BPM. Depending on the night decrease of BP 13 patients had an extreme decrease of BP (over-dipper), 12 had non-dipper pattern and 5 had dipper pattern. No relation between evaluated parameters was found. However, non-dippers showed a tendency towards lower hemodynamic and automated static perimetry parameters. Conclusions. The prevalence of HTN was 57%, while 47% demonstrated masked HTN. Lower ocular blood flow parameters and RMS according to automated static perimetry were associated with HTN. Vascular dysregulation is considered as a possible cause of RVO in young and middle-aged adults. Its manifestation is the equal frequency of non-dipper and over-dipper patterns. Ambulatory BPM in patients with RVO can be recommended for the detection of HTN, BP profiles, and indirectly, for the evaluation of ocular perfusion pressure, risk stratification and the selection of adequate and individualized antihypertensive therapy to reduce the risk of developing and progressing cardiovascular diseases and mortality.

Objective. The aim of the study was to evaluate endothelial dysfunction based on the blood concentration of endothelin 1 (ET‑1), nitric oxide (NO), serotonin (5‑HT) in essential hypertension (EHTN) in adolescents and in experimental animal models. Design and methods. The work was carried out in two stages. The clinical part was preceded by the investigation of experimental models of arterial hypertension (HTN). Twenty five immature male SHR rats aged 6–7 weeks and 10 immature male Wistar–Kyoto rats aged 6–7 weeks (control group) were examined. The clinical part of the study included 70 untreated male adolescents (mean age 15,63 ± 0,26 years), among them 24 people had a labile form of EHTN (LHTN), 30 had stable form of EHTN (SHTN), the control group included 16 subjects. All participants underwent 24-hour blood pressure monitoring. The plasma concentration of EN-1 (ET‑1) was determined by enzyme immunoassay, total concentration of stable metabolites of NO, 5‑HT in serum and platelets was measured. Results. The serum levels of ET-1 and 5-HT were higher in HTN groups than in the control group, and in adolescents with SHTN levels of both indices were higher compared to those with LHTN (p < 0,0001). Serotonin level in platelets in HTN groups was lower than in the control group (p < 0,0001). Compared to the control group, NO levels were higher in adolescents with LHTN, but lower in patients with SHTN (p < 0,0001). The changes in the level of ET‑1, 5‑HT and NO in plasma, serum and blood platelets in the experimental animal model were similar to those found in patients with labile and stable HTN. Conclusions. NO, ET‑1 and 5‑HT are early sensitive markers of endothelial dysfunction in EHTN in adolescent males, as well as in the experimental SHR rat model.

Objective. We investigated homocysteine metabolism in men with early stages of chronic kidney disease (CKD) and metabolic syndrome (MS). Design and methods. A total of 79 men were selected and divided into two groups, i. e. CKD C1–C2 degree and MS with abnormal carbohydrate metabolism (main group, n = 44) and CKD C1‑C2 degree and MS with normal carbohydrate metabolism (control group, n = 35). We assessed serum levels of fasting and postprandial glucose, HbA1c, insulin, C‑peptide, homocysteine. We also studied polymorphisms of the genes encoding homocysteine metabolism-related enzymes. Results. 82,3% patients had elevated serum levels of homocysteine with no significant differences between the groups. 90,0% cases of hyperhomocysteinemia (HHC) in men with CKD C1–C2 degree and MS were associated with polymorphism of the genes encoding homocysteine metabolism-related enzymes. In men with CKD C1–C2 degree and MS with normal carbohydrate metabolism we found positive correlations between creatinine and homocysteine (rs = 0,4; p < 0,05). Conclusions. The majority of men with MS and CKD C1–C2 degree have hyperhomocysteinemia that is usually determined by genetic factors. Serum level of homocysteine at the initial stages of renal dysfunction does not depend on the state of carbohydrate metabolism in MS.

Objective. To compare efficacy and safety of metformin monotherapy and metformin in combination with melatonin concerning the parameters of endothelial function and the vascular elasticity, arterial hypertension (HTN), vascular premature aging and sleep status in patients with metabolic syndrome (MS). Design and methods. We performed an open prospective, comparative, controlled, randomized trial in 3 parallel groups. Altogether 238 patients with MS (IDF, 2005), HTN 1–2 degrees (who reached target blood pressure (BP) with the current antihypertensive therapy) and sleep disorders (< 19 scores by the survey of subjective sleep characteristics) were randomized into 3 groups. All patients underwent a lifestyle modification, including changesin diet and physical activity, as well as the normalization of the “sleep-wakefulness” rhythm for 12 weeks. In addition, patients of the first group (n = 80) received monotherapy with metformin, patients of the second group (n = 78) received combined therapy with metformin and prolonged-release melatonin. The control group (n = 80) included patients who adhere to the lifestyle modification recommendations without any pharmacological intervention. The groups were comparable for baseline clinical and demographic characteristics. At baseline and after 12 weeks of therapy the endothelial function was evaluated by flow-dependent vasodilation. Also BP, vascular stiffness, anthropometric and metabolic parameters, adipocytokine status, vascular age, and sleep quality were assessed. Results. The results of the study confirmed the efficiency of the long-acting melatonin in combination with the standard therapy in patients with MS and circadian disorders. Melatonin normalizes the “sleep-wakefulness” rhythm. Moreover, it provides protective effect regarding endothelial function, has favorable profile of cardiovascular and metabolic effects, and slows vascular aging. No serious drug-related adverse events were registered during the follow-up. Conclusions. Melatonin supplementation to the traditional MS therapy in patients with sleep disorders is safe and effective regarding dissomnia, overweight, metabolic disorders, and also has additional benefits in terms of improvement of endothelial function, vascular stiffness, and daily BP profile.

Increasing interest to the problems of vascular ageing and need in novel parameters reflecting impact of this process on cardiovascular risk have led to the development of a concept of vascular age. Vascular age reflects cardiovascular risk. It is thought to improve cardiovascular risk prediction models and may contribute to a better understanding of cardiovascular risk, especially in young patients. The review summarizes the current knowledge on the definition, assessment and clinical significance of vascular age.