Endothelial function in normal and pathological conditions

The article presents the data on the state of endothelial function in the normally and in various diseases and conditions. The basic functions of endothelium in modulation of vascular tone, atrombogenicity and thrombogenicity of the vascular wall, regulation of vascular wall adhesion, regulation of vascular growth are described. The main causes leading to the formation of endothelial dysfunction and the mechanisms underlying it are highlighted. Numerous studies on the evaluation of endothelial function in various diseases are presented. The basic methods of drug and non-drug correction of endothelial dysfunction are presented.

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Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4353462 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Sebastian Steven ◽

Matthias Oelze ◽

Moritz Brandt ◽

Elisabeth Ullmann ◽

Swenja Kröller-Schön ◽

...

Keyword(s):

Oxidative Stress ◽

Pulmonary Hypertension ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Whole Blood ◽

Pulmonary Arteries ◽

Vascular Wall ◽

Pentaerythritol Tetranitrate ◽

Endothelin 1 ◽

Pulmonary Arterial

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined.Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells.Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

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Endothelial function and its role in the formation of cardiovascular pathology in patients with rheumatoid arthritis

Kazan medical journal ◽

10.17816/kmj2019-451 ◽

2019 ◽

Vol 100 (3) ◽

pp. 451-456

Author(s):

A A Tulichev ◽

N Yu Borovkova ◽

N N Borovkov ◽

A A Spassky ◽

I V Polyakova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Unknown Origin ◽

Vascular Wall ◽

Cardiovascular Complications ◽

Point Of View ◽

Microvascular Changes ◽

Initial Stage

Currently rheumatoid arthritis is considered as an immune inflammatory disease of unknown origin characterized by chronic erosive arthritis and systemic damage of internal organs, leading to early disability and reduced life expectancy. Cardiovascular diseases are most often mentioned as factors of poor prognosis in rheumatoid arthritis. Pathology of the cardiovascular system in rheumatoid arthritis is usually associated with the macro- and microvascular changes and rheumatoid lesions of the heart. The leading factor in the damage of the vascular wall in rheumatoid arthritis is systemic inflammation affecting its viscosity and elastic properties, increased rigidity, impaired endothelial function. Endothelial dysfunction is currently regarded to as an initial stage of morphogenesis of various vascular disorders. It is considered as a subclinical marker of cardiovascular diseases and the earliest predictor of cardiovascular complications. From this point of view study of endothelial dysfunction in patients with rheumatoid arthritis aimed at determining cardiovascular risk is a perspective direction. Only single and fragmentary information about certain endothelial functions in patients with rheumatoid arthritis and substances released in this. There is no clear analysis of relationship between them and dependence on the process activity. Not clear is their role in the pathology of the vascular wall in rheumatoid arthritis. This literature review discusses the problem of endothelial dysfunction in rheumatoid arthritis patients as well as its role in the development of cardiovascular diseases in these patients. The development mechanisms and the role of immune inflammation in its formation are considered. Also the association was found between chronic inflammatory activity indicators in rheumatoid arthritis and various biological markers and development of endothelial dysfunction. The effects of antirheumatic treatment on endothelial dysfunction in these patients were analyzed.

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Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: role of NADPH oxidase

Clinical Science ◽

10.1042/cs20100311 ◽

2010 ◽

Vol 120 (8) ◽

pp. 321-333 ◽

Cited By ~ 27

Author(s):

Rocío López-Sepúlveda ◽

Manuel Gómez-Guzmán ◽

Maria José Zarzuelo ◽

Miguel Romero ◽

Manuel Sánchez ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Nadph Oxidase ◽

Endothelial Function ◽

Oxidase Activity ◽

Red Wine ◽

Vascular Wall ◽

Nadph Oxidase Activity ◽

Wine Polyphenols ◽

Red Wine Polyphenols ◽

O2 Production

RWPs (red wine polyphenols) exert antihypertensive effects and improve endothelial function by reducing the plasma levels of ET-1 (endothelin-1) and the subsequent vascular production of O2•− (superoxide anion). Our present study was designed to evaluate whether RWPs act directly in the vascular wall improving endothelial dysfunction and O2•− production induced by ET-1 and to analyse the compounds responsible for these protective effects. We incubated rat isolated aortic rings in the presence or absence of ET-1 (10 nM) and RWPs (10−4 to 10−2 g/l) or catechin (0.2 μM), epicatechin (10 μM) and resveratrol (0.1 μM). ET-1 reduced the relaxant responses to acetylcholine, increased intracellular O2•− production, NADPH oxidase activity and protein expression of NADPH oxidase subunit p47phox. All these changes were prevented by RWPs. The preventive effects of RWPs were unaffected by co-incubation with either ICI-182780, an ER (oestrogen receptor) antagonist, or GW9662, a PPARγ (peroxisome-proliferator-activated receptor γ) antagonist. RWPs inhibited the phosphorylation of the mitogen-activated protein kinase, ERK1/2 (extracellular signal-regulated kinase 1/2), a key regulator of p47phox expression in response to ET-1. When the isolated polyphenols were tested, at the concentrations found in 10−2 g/l RWPs, only epicatechin prevented endothelial dysfunction and all biochemical changes induced by ET-1 in the vascular wall. Taken together, these results indicate that RWPs prevent ET-1-induced vascular O2•− production by reducing overexpression of p47phox and the subsequent increased NADPH oxidase activity, leading to improvement in endothelial function. The effects of RWPs appear to be independent of ER and PPARγ activation and are related to ERK1/2 inhibition.

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Antioxidant therapy of endothelialdysfunction

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf11114-25 ◽

2013 ◽

Vol 11 (1) ◽

pp. 14-25 ◽

Cited By ~ 2

Author(s):

Ivan Nikolayevich Tyurenkov ◽

Andrey Vladislavovich Voronkov ◽

Anna Albertovna Sliyetsans ◽

Yelena Grigoryevna Dorkina ◽

Grigoriy Leonidovich Snigur

Keyword(s):

Oxidative Stress ◽

Clinical Practice ◽

Free Radical ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Antioxidant Therapy ◽

Free Radical Processes ◽

Pathological Conditions ◽

Radical Processes

The survey provides data on the broad participation of free radical processes in the pathogenesis of various pathological conditions, including in endothelial dysfunction, which necessitates the prevention and correction of such violations. Under these conditions pathogenetically justified is the use of antioxidants in clinical practice from various pharmacological groups as affecting oxidative stress, they have the potential to improve endothelial function, acting as endotelioprotektors.

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Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

International Journal of Molecular Sciences ◽

10.3390/ijms21093048 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3048 ◽

Cited By ~ 1

Author(s):

Marina M. Ziganshina ◽

Ekaterina L. Yarotskaya ◽

Nicolai V. Bovin ◽

Stanislav V. Pavlovich ◽

Gennady T. Sukhikh

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

Vascular Tone ◽

Endothelial Activation ◽

Endothelial Glycocalyx ◽

Pathogenic Factor ◽

New Approach ◽

Pathological Conditions ◽

Key Factor ◽

Regulation Of Vascular Tone

Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.

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Abstract 14050: The Gut Flora Promotes Endothelial Dysfunction Through Vascular MicroRNA-204-mediated Down-regulation of Endothelial Sirtuin1

Circulation ◽

10.1161/circ.130.suppl_2.14050 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Ajit Vikram ◽

Young-Rae Kim ◽

Santosh Kumar ◽

Julia S Jacobs ◽

Kaikobad Irani

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

High Fat Diet ◽

Ex Vivo ◽

Vascular Wall ◽

High Fat ◽

Gut Flora ◽

Atherosclerotic Vascular Disease ◽

Germ Free

The gut flora contributes to development of atherosclerosis. Endothelial dysfunction, one manifestation of which is impaired endothelium-dependent vasorelaxation, accompanies and promotes atherosclerotic vascular disease. Here we show that gut flora impair endothelium-dependent vasorelaxation by remotely up-regulating microRNA-204 (miR-204) which downregulates SIRTUIN1 (SIRT1) in the vascular wall. Microarray analysis in aortas of germ-free mice revealed a set of down-regulated microRNAs, including miR-204, which target SIRT1. Suppression of gut flora in mice with antibiotics in drinking water decreased aortic miR-204, increased aortic SIRT1, and improved endothelium-dependent vasorelaxation, effects that were reversed with discontinuation of antibiotics. In addition, miR-204 mimic impaired endothelium-dependent aortic vasorelaxation ex vivo. Moreover, high-fat diet feeding stimulated aortic miR-204, suppressed SIRT1, and impaired endothelial function, all of which were mitigated by administration of antibiotics, and reversed with stoppage of antibiotics. In contrast, antibiotics did not improve high-fat diet-induced endothelial dysfunction in mice conditionally lacking endothelial SIRT1. In addition, anti-miR-204 delivered systemically prevented high-fat diet-induced endothelial dysfunction and vascular SIRT1 decrease. Finally, serum from mice on antibiotics suppressed miR-204, and increased SIRT1, in endothelial cells, effects that were not observed with serum from mice in which antibiotics were discontinued. Therefore, the gut flora remotely downregulates endothelial SIRT1 through miR-204, leading to impairment of endothelial function.

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Novel Biomarkers of Endothelial Dysfunction in Cardiovascular Diseases

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-08-08 ◽

2021 ◽

Vol 17 (4) ◽

pp. 612-618

Author(s):

Z. M. Abdurakhmanov ◽

B. Y. Umarov ◽

M. M. Abdurakhmanov

Keyword(s):

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Classical Method ◽

Physiological State ◽

The State ◽

Sensory Nerves ◽

Advantages And Disadvantages ◽

Cellular Marker ◽

New Biomarkers

The review analyzes the role of assessing the state of the endothelium in the onset and progression of cardiovascular diseases, stratification of their risks, since endothelial dysfunction (ED) is a crucial predictor of this pathologies. In this regard, this paper presents the modern understanding of the methods for assessing ED, presents the advantages and disadvantages of various techniques. Despite the fact that flow-mediated dilation is widely used as a classical method for studying endothelial function, this technique depends on the physiological state of sensory nerves and calcium-activated potassium channels, cardiac output. This review focuses on new biomarkers for ED such as endothelial microparticles, endoglin and endocan, and discusses the relevance of the criteria for their use in clinical practice. Based on current scientific advances, the authors concluded that among these three newest biomarkers, today, endocan can be considered a more informative and reliable cellular marker of ED. Moreover, the authors have shown that when measured separately, many of the studied classical circulating biomarkers do not provide reliable information about the state of the endothelium, since the endothelial function has a complex physiological nature which therefore raises the question of the advisability of considering a combination of classical and new biomarkers for improving the assessment of the endothelial state.

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Features of stress-regulating system changes in adolescents with cardiovascular pathology at endothelial dysfunction

Modern pediatrics. Ukraine ◽

10.15574/sp.2020.109.8 ◽

2020 ◽

pp. 8-14

Author(s):

D. Kashkalda ◽

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Normal Function ◽

The State ◽

Vascular Pathology ◽

Antioxidant Systems ◽

Vascular Endothelial ◽

System Changes ◽

Endothelial Response

Relevance. Endothelial dysfunction serves as a starting mechanism for any vascular pathology and its progression. The state of endothelial function is greatly influenced by stress, however, the study of the features of the functioning of stress-regulating systems in adolescents with cardiovascular disorders has practically not been studied. Objective: to investigate stress-regulating system changes in adolescents with cardiovascular disease at endothelial dysfunction. Materials and methods. A total of 73 adolescents (49 boys and 24 girls) with cardiovascular disease (CVD) aged 12–18 were surveyed. The adolescents were divided into 3 groups: those with normal endothelial function, those with endothelial dysfunction and those with paradoxical vascular endothelial response. Stress regulation is dominated by stress- realizing and stress-limiting systems. The state of stress-realizing systems was assessed by the level of cortisol, malondialdehyde, carbonylated proteins (CP) in blood serum and catecholamines (CA) in urine; stress-limiting systems — by the level of glutathione peroxidase (GPO), superoxide dismutase (SOD), serotonin in the blood and melatonin in urine. Results. In adolescents with endothelial dysfunction and paradoxical vascular endothelial response, there was a regulatory imbalance of key antioxidant enzymes (SOD and GPO) and a decrease in serotonin levels. In endothelial vascular dysfunction, changes in stress-regulatory systems are more pronounced in girls. The revealed correlation relations of the studied indicators in adolescents with normal function and vascular endothelium dysfunction emphasize strong links between monoamines (CA and melatonin), enzymatic (GPO) tension and activation of non-enzymatic (melatonin) links of antioxidant system. Conclusion. In adolescents with a non-inflammatory pathology of CVD, endothelial function depends on the activation and interaction of stress-regulating systems. With vascular endothelial dysfunction, changes in the content of monoamines and indicators of the pro- and antioxidant systems have gender differences, indicating stress-limiting stress and activation of stress-realizing systems in girls. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: adolescents, cardiovascular system, endothelial function, stresslimiting indicators, stressrealizing indicators.

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INFLUENCE OF THE TRANSFERRED SYPHILITIC INFECTION ON THE COURSE OF PREGNANCY, CHILDBIRTH AND THE STATE OF NEWBORNS

Wiadomości Lekarskie ◽

10.36740/wlek201902106 ◽

2019 ◽

Vol 72 (2) ◽

pp. 175-180

Author(s):

Viacheslav M. Husiev ◽

Daria S. Khapchenkova

Keyword(s):

Pregnant Women ◽

Vascular Wall ◽

Main Group ◽

The State ◽

Control Group ◽

Perinatal Complications ◽

Pregnancy And Childbirth ◽

Pathological Conditions ◽

Intrauterine Hypoxia ◽

History Of

Introduction: The article presents information about the peculiarities of the course of pregnancy and childbirth in women with a syphilitic infection in the anamnesis. The peculiarities of the state of newborn babies born from mothers who have suffered syphilis are described. To date, the incidence of syphilis in Ukraine has a clear tendency to decline, but still remains quite high. The maximum incidence of syphilis is observed in women aged 15-20 years. The combination of pregnancy and syphilitic infection in an anamnesis is an unfavorable factor in regard to high risk of perinatal complications, the frequency of which does not tend to decrease. The aim - study the features of the course of pregnancy and childbirth in women with a syphilitic infection in the anamnesis, the evaluation of the state of newborns. Materials and methods: A prospective examination of 57 healthy women and their newborns (control group) and 60 pregnant women with a history of syphilitic infection (the main group) had been conducted. All pregnant women had undergone ultrasound examination, including feto- and placentometry, an estimate of the amount of amniotic fluid. The effect of the transferred syphilis on the state of the newborn had been assessed in accordance with the results of the clinical examination of an anthropometric data, including an Apgar score. Results: It is stated that the incidence of latent (41,66%) and forms with a prolonged course (20,00%) of syphilitic infection. The threat of premature childbirth was almost 3,5 times higher than in women with syphilis, cases of an anemia in pregnant women – 2 times, hypertensive disorders of pregnant women were 2,4 times more common in women of the main group, fetal development retardation syndrome 6,4 times, while a greater percentage of this disorder was recorded among women in the main group who were ill with latent forms and suffered secondary recurrent syphilis (35%). In 20% of the cases, pregnancy in women with syphilis has been completed by the cesarean section, an abnormality of the contractile capacity of the uterus was significantly higher – 23,33%. The adaptive capacity of the newborns in the main group has been significantly lower, compared to the control group. Conclusions: Syphilitic infection in the anamnesis complicates the course of pregnancy with numerous pathological conditions. Syphilitic infection, borne before pregnancy, affects not only the course of pregnancy, but also the course of childbirth and the postpartum period. The pathological conditions in infants are due to a decrease in resistance to birth stress, early depletion of adaptive resources of newborns under the influence of a syphilitic infection of the mother. In children who have experienced chronic intrauterine hypoxia, the risk of hemorrhagic syndrome is significantly higher due to increased permeability of the vascular wall. Such children have a tendency to develop neurological disorders and respiratory system lesions.

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Role of oxygen in fetoplacental endothelial responses: hypoxia, physiological normoxia, or hyperoxia?

AJP Cell Physiology ◽

10.1152/ajpcell.00528.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. C943-C953 ◽

Cited By ~ 2

Author(s):

Chi Zhou ◽

Qing-yun Zou ◽

Yi-zhou Jiang ◽

Jing Zheng

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Current Knowledge ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Vascular Growth ◽

Adverse Pregnancy ◽

Underlying Mechanisms ◽

Cells Cultured

During pregnancy, placental vascular growth, which is essential for supporting the rapidly growing fetus, is associated with marked elevations in blood flow. These vascular changes take place under chronic physiological low O2 (less than 2–8% O2 in human; chronic physiological normoxia, CPN) throughout pregnancy. O2 level below CPN pertinent to the placenta results in placental hypoxia. Such hypoxia can cause severe endothelial dysfunction, which is associated with adverse pregnancy outcomes (e.g., preeclampsia) and high risk of adult-onset cardiovascular diseases in children born to these pregnancy complications. However, our current knowledge about the mechanisms underlying fetoplacental endothelial function is derived primarily from cell models established under atmospheric O2 (~21% O2 at sea level, hyperoxia). Recent evidence has shown that fetoplacental endothelial cells cultured under CPN have distinct gene expression profiles and cellular responses compared with cells cultured under chronic hyperoxia. These data indicate the critical roles of CPN in programming fetal endothelial function and prompt us to re-examine the mechanisms governing fetoplacental endothelial function under CPN. Better understanding these mechanisms will facilitate us to develop preventive and therapeutic strategies for endothelial dysfunction-associated diseases (e.g., preeclampsia). This review will provide a brief summary on the impacts of CPN on endothelial function and its underlying mechanisms with a focus on fetoplacental endothelial cells.

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