Diagnosis Of Endothelial Dysfunction Research Articles

Mitochondrial dysfunction in the pathogenesis of endothelial dysfunction.

Cardiovascular diseases (CVDs) are a matter of concern worldwide, and mitochondrial dysfunction is one of the major contributing factors. Vascular endothelial dysfunction has a major role in the development of atherosclerosis because of the abnormal chemokine secretion, inflammatory mediators, enhancement of LDL oxidation, cytokine elevation, and smooth muscle cell proliferation. Endothelial cells transfer oxygen from the pulmonary circulatory system to the tissue surrounding the blood vessels, and a majority of oxygen is transferred to the myocardium by endothelial cells, which utilise a small amount of oxygen to generate ATP. Free radicals of oxide are produced by mitochondria, which are responsible for cellular oxygen uptake. Increased mitochondrial ROS generation and reduction in agonist-stimulated eNOS activation and nitric oxide bioavailability were directly linked to the observed change in mitochondrial dynamics, resulting in various CVDs and endothelial dysfunction. Presently, the manuscript mainly focuses on endothelial dysfunction, providing a deep understanding of the various features of mitochondrial mechanisms that are used to modulate endothelial dysfunction. We talk about recent findings and approaches that may make it possible to detect mitochondrial dysfunction as a potential biomarker for risk assessment and diagnosis of endothelial dysfunction. In the end, we cover several targets that may reduce mitochondrial dysfunction through both direct and indirect processes and assess the impact of several different classes of drugs in the context of endothelial dysfunction.

Endothelial dysfunction in the mother–placenta–fetus system after a new coronavirus infection SARS-CoV-2: An open prospective cross-sectional study

Background. Generalized endotheliopathy in SARS-CoV-2 is associated with the release of the vasoactive peptide endothelin-1, which stimulates the activation of both the plasma and platelet clotting pathways. It is believed that endothelin-1 is one of the most potent vasopressors of the human cardiovascular system and has a strong pressor and thrombogenic effect on many vessels, including in the motherplacentafetus system.
 Aim. To study endothelial dysfunction in pregnant women with new coronavirus infection SARS-CoV-2.
 Materials and methods. An open-label prospective continuous cross-sectional study enrolled 96 patients who survived COVID-19 at various gestational ages. Depending on the severity of the underlying disease, patients were divided into groups: Group 1 (n=18) included patients with mild SARS-CoV-2 coronavirus infection, Group 2 (n=56) included women with moderate severity, Group 3 (n=22) included patients with severe COVID-19. The control group consisted of 100 pregnant women who had no COVID-19 or signs of acute respiratory viral infection. In all groups, endothelin-1 levels were determined by enzyme-linked immunosorbent assay.
 Results. In pregnant women with no COVID-19 and patients after mild COVID-19, the level of endothelin-1 corresponds to the reference values; in pregnant women with moderate and severe underlying disease, the level of endothelin-1 was 2.04.0 pmol/L. It reflects the increased activity of the endothelium in the uterine bloodstream and blood vessels in the motherplacentafetus system. Placental insufficiency in women after COVID-19 is caused by endothelial dysfunction that triggers vasospasm and increased vascular resistance in the uterine arteries (r=0.8; p0.01).
 Conclusion. The diagnosis of endothelial dysfunction in the motherplacentafetus system after COVID-19 can be helpful in the prediction and prevention of vascular complications, both placental, associated with great obstetrical syndromes (premature birth, intrauterine growth retardation, preeclampsia, antenatal fetal death), and extraplacental ones (arterial and venous thrombosis).

Features of cardiometabolic disorders in obesity on the example of the children’s population of the Rostov region

Objective: to study the features of the blood lipid profile in obese children and adolescents, depending on the presence of insulin resistance, endothelial dysfunction and minimal diastolic dysfunction of the left ventricle. Materials and methods: the study involved 370 obese children and adolescents from 7 to 17 years of age (the main group) with a body mass index BMI > 30, the control group consisted of 123 children of the same age without obesity. Methods: clinical, paraclinical (biochemical blood test, blood pressure measurement, functional diagnosis of endothelial dysfunction, assessment of minimal diastolic dysfunction). Results: cardiometabolic disorders in obesity in childhood and adolescence are accompanied, first of all, by hypertriglyceridemia, which entails further violations of the lipid profile. There was also a positive correlation between changes in insulin and triglyceride levels in children and adolescents with obesity and endothelial dysfunction, as well as in patients with HOMA IR 3.2 and a combination of endothelial dysfunction and minimal dysfunction. Conclusions: based on the study of the nature of lipid spectrum disorders in obese children and adolescents and the presence of signs of endothelial dysfunction and/or minimal left ventricular dysfunction, it was concluded that obesity at this age is more often accompanied by minimal left ventricular diastolic dysfunction or a combination of endothelial dysfunction and left ventricular dysfunction. The development of insulin resistance leads to an increase in the combined pathology (ED and MDLj). Hypertriglyceridemia, which is associated with high levels of insulin and presumably determines the development of insulin resistance, plays an important role in the development of cardiometabolic disorders in obesity in childhood and adolescence.

Endothelial Dysfunction Diagnostic “Platform” in patients with diabetes mellitus

Objective: to determine the diagnostic signifi cance of endothelial dysfunction (ED) laboratory markers.Material and methods: we examined 276 men with type 2 diabetes mellitus (age 54.0[49;60] years). Patients underwent general clinical studies, analysis of carbohydrate and lipid metabolism parameters, adipohormones: leptin, resistin, adiponectin. Endothelial function was assessed by ultrasound examination of endothelium-dependent vasodilation (EDVD) of the brachial artery during a test with reactive hyperemia and determination of biochemical parameters of endothelial function — nitric oxide (NO), endothelial synthase NO type3, endothelin, ICAM-1, VCAM-1, p- and e-selectins, cadherin, PAI-1, VEGF-1, homocysteine B, C-reactive protein (CRP), osteoprotegerin. To assess the diagnostic signifi cance of the methods and to determine the cut-off , ROC analysis was used.Results: independent signifi cance in the diagnosis of ED was demonstrated by NO, ICAM-1, resistin (p<0.001), CRP (p=0.006). Th e odds ratio of ED for resistin was 6.97, which is 1.9 times higher than NO and ICAM-1 and 3.7 times higher than CRP. Th e cut-off for diagnostic of ED are: NO — 97.3 μmol/L, ICAM-1 — 309.4 ng/ml, resistin — 6.32 ng/ml, CRP — 6.25 mg/L.Conclusion: the diagnostic platform for determining ED, along with the ultrasound assessment of EDVD, should include the analysis of its biochemical markers: NO, ICAM-1, resistin, CRP. Resistin is an independent, high-precision marker of ED, which is the pathogenetic link between endothelial dysfunction and adipose tissue dysmetabolism.

Эректильная дисфункция сосудистого генеза: комплексный подход к диагностике

Introduction. Erectile dysfunction (ED) combines many conditions leading to erectile dysfunction and disability to perform sexual intercourse. It was confirmed that the most common cause of ED is vascular disorders, primarily associated with atherosclerosis that leads to cardiovascular diseases. Objective. To analyze the available literature data about the methods for diagnosis vascular ED, including according to cardiovascular system status. Materials and methods. The results of the search in scientific databases Medline, EMBASE, Cochrane, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Elibrary.ru were analyzed. After a detailed verification of the reliability of sources, impact factors of journals and the sequence of presentation of the material, 63 most relevant scientific publications were selected directly for citation. Results. The first step of the vascular ED diagnosis is the monitoring of nocturnal penile tumescences. Next, the risk factors for cardiovascular diseases and ED are evaluated: anamnesis of elevated blood pressure, physical activity, smoking, body weight, measurement of blood pressure, blood analysis with the lipid and glycemic profiles. For the diagnosis of endothelial dysfunction (END), the determination of flow-dependent vasodilation of the brachial artery is used, with the possible determination of the rate of blood filling after decompression. After the END is confirmed in patients with ED, it is useful to determine the vascular age using the SCORE scale. For further management of the patient with ED and END, stratification of the associated with sexual activity cardiovascular complications risk is recommended. Conclusion. The proposed diagnostic algorithm will allow not only identify the vascular component of ED at an early stage, but also to avoid fatal cardiovascular complications by prescribing and recommending therapeutic and preventive measures to patients with asymptomatic cardiovascular diseases.

Profile of new vascular damage biomarkers in middle-aged men with arterial hypertension

PurposeNormal endothelial function is important for the homeostasis of the cardiovascular (CV) system. The aim of the present study was to determine the profile of key parameters of endothelial dysfunction in middle-aged men that play a significant role in the functioning of endothelial vessels, which seems to be crucial for the early diagnosis of cardiovascular disorders. Materials and methodsThe study included 53 men, 20 with hypertension (HTN), 18 with HTN and related diseases, 15 healthy controls Apart from general testing (BMI, biochemical analysis, SBP, DBP), we used the Griess reaction to assess the total amount of nitric oxide (NO), and used ELISA to verify the concentrations of malondialdehyde (MDA), nitrotyrosine (NT), asymmetric dimethylarginine (ADMA), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and myeloperoxidase (MPO). Furthermore, we assessed the concentration of circulating free DNA (cfDNA) using the fluorescence method. ResultsThe values of MDA, ADMA, cfDNA, and MPO observed in samples from men with HTN were determined to be higher compared to those from men without HTN. In the group of men with HTN and other concomitant cardiovascular disorders, we observed low concentrations of NO, MDA, and ADMA with high concentrations of cfDNA. ConclusionsThe results obtained for parameters selected for the study, should be considered by cardiologists as a prompt to include in the diagnostic profile the assessment of NO and cfDNA concentrations for risk evaluation and/or diagnosis of endothelial dysfunction in patients suffering from HTN or related complications.

Nitric Oxide Production in Professional Skiers During Physical Activity at Maximum Load.

The purpose of this study is to assess the production of nitric oxide in professional cross-country skiers with normotensive and hypertensive responses to physical activity at maximum load. The observation group included professional cross-country skiers (22.2 ± 7.1 years, = 107) who were current members of the national team of the Komi Republic. All the examined athletes performed the exercise test on a cycle ergometer “until exhaustion.” The following parameters were determined for each participant while they were sitting at rest, while at their anaerobic threshold level, during peak load, and during the recovery period (5th min): systolic blood pressure, diastolic blood pressure, heart rate, and the level of stable nitric oxide metabolites (nitrites, nitrates) in capillary blood samples. According to the blood pressure results, the cross-country skiers were divided into two groups. Group I included athletes with a normotensive response to stress. Group II was composed of individuals with a hypertensive response to stress. During the performance of the test “until exhaustion,” a significant (p < 0.05) increase in the amount of stable metabolites of nitric oxide was observed in the group of athletes with a normotensive response to the load compared with the group with a hypertensive response to the load. In athletes with a normotensive reaction to the load during exercise at maximum load and in the early recovery period, nitrate was prioritized in the regulation of vascular tone. The exercise test on a cycle ergometer “until exhaustion,” combined with the assessment of the levels of stable nitric oxide metabolites in plasma, can be considered a test for the early diagnosis of endothelial dysfunction in professional athletes.

Soluble forms of adhesive molecules in blood serum as a marker of endothelial dysfunction in chronic generalized parodontitis.

An important factor in the pathogenesis of chronic inflammation in periodontitis is endothelial dysfunction (ED). Adhesion molecules are markers of impaired barrier function, adhesive properties and vascular permeability. The study of the concentration of soluble adhesion molecules is very promising in the diagnosis of ED. The purpose of this research was to study changes in the concentration of soluble forms of adhesive molecules of the selectin family and the immunoglobulin superfamily when used as markers of systemic manifestations of ED in the dynamics of the treatment of chronic generalized periodontitis (CP) using surgical and therapeutic schemes. 60 patients with CP (33 women and 27 men) and 20 clinically healthy volunteers (10 men and 10 women) were examined. The state of the endothelium was assessed by the content in the serum of soluble forms of adhesive molecules - sP- and sE-selectins, intercellular adhesive molecules of type 1 (sICAM-1), vascular molecules of cell adhesion of type 1 (VCAM-1) by ELISA. The short-term results of non-surgical treatment of CP are more effective in correction of vascular wall adhesive properties disorders compared with surgical treatment. Conservative treatment of chronic hepatitis C effectively adjusted the blood content of adherent endothelium molecules in women than in men. The long-term results of applying this scheme were characterized by partial preservation of a positive effect on the adhesive properties of the endothelium, however, long-term results were inferior to short-term ones. Surgical treatment of CP in women in the early postoperative period was accompanied by reactive impairment of the adhesive properties of the endothelium. The long-term results of this treatment regimen testified to its greater effectiveness. In women, the effectiveness of treatment of CP in restoring the adhesive properties of the endothelium was higher than in men. The results obtained allow us to conclude that the systemic manifestations of ED in CP were characterized by an increase in the concentration in the blood of soluble forms of adhesion molecules. The dynamics of the concentration of adhesive molecules during the treatment of СР testified to the dependence of the sex of patients on the effectiveness of the influence of therapeutic and surgical treatment regimens on the systemic manifestations of ED.

Structural and functional peculiarities of the endothelium of heart vessels of mature rats according to immunistochemical studies

The relevance of the study is connected with the modern point of view that endothelial dysfunction may be the cause of such socially significant diseases as atherosclerosis, diabetes, varicose veins, etc. The aim of the work is to study the morphofunctional peculiarities of the endothelium of the cardiovascular vessels of the mature rat using Willebrand factor (vWF) immunohistochemistry.Material and methods. We used mature Wistar rats (n = 12). Polyclonal rabbit antibodies were used for the immunohistochemical detection of vWF. The reaction was carried out on paraffin sections, made through the whole heart.Results. It was shown that the immunopositive reaction to vWF (vWF+ ) in the endothelium of different regions of the rat heart is not uniform. A tendency was found to weaken the vWF+ reaction in the direction from the base of the heart to its apex. Most functionally active endothelial cells with signs of exocytosis were observed in the aortic root, the large coronary arteries of the epicardium, the fibrous ring, the valves and the subaortal cone. vWF+ was less pronounced in the endothelium lining the atrial and ventricular cavities and in the myocardial capillaries.Conclusions. Using immunohistochemical detection of the vWF, the endothelium features of different parts of the rat heart were identified. Structural features due to increased secretion of vascular endothelial cells of the heart were revealed. Further research in this direction may be important to explain the mechanisms and diagnosis of endothelial dysfunction.

Endothelial Dysfunction in Vascular Encephalopathy

This review addresses endothelial dysfunction as a component in the pathogenesis of vascular encephalopathy (VE), which is particularly severe in lesions of the small cerebral vessels. The authors consider the possible mechanisms of impairment of endothelial function in VE and the characteristics of the neuroanatomy and pathophysiology of the endothelium of the cerebral vessels. Laboratory and instrumented methods for the diagnosis of endothelial dysfunction are discussed, along with approaches to its correction.

Plethysmographic and Biochemical Markers in the Diagnosis of Endothelial Dysfunction in Pediatric Acute Lymphoblastic Leukemia Survivors – New Applications

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

Вивчення функціонального стану ендотелію за допомогою комплексу показників проби з реактивною гіперемією

Diagnosis of endothelial dysfunction is a key point in the prevention and treatment of cardiovascular diseases. In scientific research the study of the state of the endothelium used test with reactive hyperemia of brachial artery wich present as the value of endothelium dependent and independent artery dilatation. However, the disadvantage of this marker is ignoring the size of arteries, well know that small arteries has a greater degree of dilation more than big arterias, this fact making difficult to compare results between different patients.The aim of our study was to examine the state of endothelium using a complex of markers, compare them informative in children with JRA who are at risk for the development of endothelial dysfunction.Materials and Methods. The study was included 40 children with juvenile rheumatoid arthritis who were treated at the department of children's cardiorheumatology Kyiv City Children's Hospital #1 and Kiev Regional Hospital m. Boyarka.Results. The study found a development of endothelial dysfunction changes in endothelium dependent vasodilation, reactive hyperemia and coefficient of vasodilation. Simultaneous marked change of endothelium vasodilation of the brachial artery and coefficient of vasodilatation. There were no pathological changes in endothelial shear stress in patients compared with healthy children.Conclusions. Evaluate the state of the endothelium is necessary with the help of a set of indicators (RH, EDVD, VC) that will help to avoid diagnostic mistakes during the test with the reactive hyperemia.Key words: endothelial dysfunction, reactive hyperemia, endothelium dependent vasodilation, tension shear, coefficient of vasodilation.

Cardiovascular Risk Factors in Chronic Inflammatory Rheumatic Diseases: Modern Assessment and Diagnosis

The current view is that systemic inflammation, which is specific to all chronic inflammatory rheumatic diseases (CIRD), accelerates atherogenesis; this hypothesis is supported by the high cardiovascular (CV) morbidity and mortality rates and the high prevalence of all atherosclerosis stages and complications in CIRD patients. The assessment of traditional CV risk factors underestimates the actual risk in patients with CIRD. A comprehensive evaluation and follow-up of both traditional and non-traditional CV risk factors, as well as the correct classification of risk reduction categories are necessary. Imaging techniques (e.g. carotid intima-media thickness and flow-mediated vasodilation) can be used for the early diagnosis of endothelial dysfunction. Immunologic and metabolic markers (anti-cyclic citrullinated peptide (CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, proinflammatory cytokines, TH0/TH1 lymphocytes and homocysteine) may be involved in the atherosclerotic disease development specific to CIRD. A modern therapeutic approach should include the early diagnosis of endothelial dysfunction and atherosclerosis, treatment of CIRD, specific medication designed to control atherosclerosis, changes in patient lifestyle and periodic follow-ups. The assessment and diagnosis of traditional and non-traditional CV risk factors, followed by aggressive prevention and therapy, are necessary to achieve efficient control over the inflammation, immunologic and metabolic disorders specific to CIRD.

Evaluation of microvascular reactivity with laser Doppler flowmetry in chronic kidney disease

Cardiovascular diseases are the major causes of mortality in patients with chronic kidney disease (CKD). The complex process of accelerated athero- and arteriosclerosis in CKD is associated with this phenomenon, where endothelial dysfunction (ED) is one of the initial steps. Hence, the early diagnosis of ED can potentially lead to early interventions which could result in a better outcome for these patients. Several methodologies have been developed for the diagnosis of ED. Laser Doppler flowmetry (LDF) enables us to study the microcirculation continuously in a non-invasive manner. In our review we would like to focus on different tests developed for LDF, like postocclusive reactive hyperaemia, local heating, iontophoresis, microdialysis or analysis of flowmotion. We would also like to summarize the available data in CKD with these methodologies to enlighten their perspectives in the clinical use on this patient population.

Early (preclinical) diagnosis of endothelial dysfunction and disturbed vegetative regulation in young men with atherosclerosis risk factors (based upon the examination of male students of Tomsk universities)

Early (preclinical) diagnosis of endothelial dysfunction and disturbed vegetative regulation in young men with atherosclerosis risk factors (based upon the examination of male students of Tomsk universities)