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We studied the effect of molecular hydrogen H2 on the content of circulating endothelial cells and the macrohistological structure of the heart in rats with simulated chronic heart failure. Inhalation with 2% H2 was carried out repeatedly (40 min per day for 5 consecutive days) or once (40 min). Molecular hydrogen inhalations in both regimens caused a decrease in the number of circulating endothelial cells; the most pronounced effect was observed after repeated inhalations on day 14 after chronic heart failure modeling. The decrease in the count of circulating endothelial cells under the action of H2 was accompanied by recovery of the myocardial structure and a decrease in its weight. Molecular hydrogen in chronic heart failure limited the damage to endothelial cells and improved the structure of rat myocardium, which allows us to consider H2 inhalations as the means reducing the progression of chronic heart failure. [ABSTRACT FROM AUTHOR]

A comparative assessment of the expression of the mitochondrial fission marker Drp1 and the autophagy marker LC3 in neurons and endothelial cells in the hippocampus and entorhinal cortex during progression of cognitive deficit was performed in animals with intrahippocampal administration of β-amyloid. In both brain regions, the expression of Drp1 and LC3 in neuronal and endothelial cells was enhanced. The peak of cognitive impairment corresponded to the maximum expression of Drp1 and LC3 in hippocampal neurons and was preceded by an increase in the number of Drp1+ and LC3+ endothelial cells in this brain region. These data attests to a possible role of aberrant mitochondrial dynamics and autophagy of endothelial cells in the impairment of brain plasticity in the Alzheimer's type neurodegeneration. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus induces the expression of VCAM-1, P- and E-selectins on the endothelial cells of the EA.hy926 cell line but, at the same time, causes the significant suppression of the force and work of adhesion between these receptors of endotheliocytes and the receptors of neutrophils in an experimental septicemia model. Adhesion contacts between the receptors of neutrophils and endotheliocytes are statistically significantly suppressed under non-opsonized and opsonized S. aureus treatment, which disrupts the initial stage of transendothelial migration of neutrophils—adhesion. Thus, S. aureus causes the arrest of neutrophils in the bloodstream in an experimental septicemia model. [ABSTRACT FROM AUTHOR]

Burn injury is an important medical problem, as it is accompanied by high mortality rates in burn shock. Aim of the study was to conduct an ultrastructural stereological analysis of changes in the blood microvessels of the left ventricular myocardium in burn shock.Material and methods. Myocardial samples during the early section were collected 2 hours after the detection of biological death in the victims from severe burn shock (3 men and 2 women); age group 32-44 years. An ultrastructural study of endothelial cells of the microvasculature of the left ventricular myocardium was carried out.Results and discussion. The development of severe burn shock is accompanied by changes in the ultrastructure of the endothelial cells of the blood microvessels of the left ventricular myocardium, which is associated with intracellular degradation and exocytosis. These ultrastructural changes may indicate impairment of vesicular transport in the endothelium of the myocardial microvessels in burn shock. A feature of the ultrastructure of the endothelium was the heterogeneity of the endothelial cells of the blood capillaries due to the revealed dark and light endothelial cells, which differ in the saturation of the cytoplasm with organelles. The new data obtained on changes in the ultrastructure of the endothelium of the microvasculature of the left ventricular myocardium can be informative in the development of approaches to intensive therapy of cardioprotective direction in combustiological patients with burn shock.

A close relationship between the brain capillaries and the functional load of neurons and glial cells allows considering them as a single structural and functional complex, a neurovascular unit (NVU). The effects of lipopolysaccharide (LPS, 5–30 µg/mL, 24h) on nitric oxide (NO) production and of menadione (5–50 µM, 24 h) on cell viability in cultures of granule neurons, cerebrovascular endothelial cells and astrocytes, as well as the state of mitochondria (Mt) in different NVU cell types, were assessed. It was found that the application of 5 µg/mL of LPS caused an intense NO production in cell cultures. The largest effect was shown for astrocytes, in which LPS caused a significant increase in NO production by more than 8-fold. In cultures of granule neurons, this exposure caused an almost 5-fold increase in NO production. The weakest response to the stimulation of NO production was shown for endotheliocytes, 1.7-fold. To induce oxidative damage, menadione was introduced into a culture medium. In neuronal cultures, 10 µM of menadione was already enough to cause complete death of granule neurons. Damage to endotheliocytes and astrocytes was only observed when the menadione concentration increased up to 50 µM. Since menadione-induced oxidative stress is mediated by mitochondria, the state of the Mt was assessed in intact cells. In astrocytes and endotheliocytes, Mt were numerous and represented long curved strands, whereas in granule neurons, these organelles are much smaller in size and have a rounded shape. Thus, in the NVU, astrocytes are the main NO producers during neuroinflammation, while neurons are the most sensitive to oxidative stress despite relatively poor development of the mitochondrial network; cerebrovascular endothelial cells demonstrated a minimum contribution to NO production. [ABSTRACT FROM AUTHOR]

The molecular action of vasopressin depends on the localization of hormonal receptors. The basic physiological effects of vasopressin are manifested in the blood vasculature, renal inner medulla and brain. To date, new information concerning the tissue-specific spreading of vasopressin receptors has been accumulated, and it needs to be summarized. Platelets and endotheliocytes expressing V1a and V2 receptor types, respectively, are related to less investigated targets of the hormone. Vasopressin induces the initial reversible stage of platelet activation, required for interaction with intercellular matrix proteins. Platelet adhesion on endothelium activates cellular secretion of growth factors and enzymes for intercellular matrix glucosamine metabolism. Platelet hyaluronidase HYAL2 hydrolyses high-molecular hyaluronic acid to shorter fragments. Unlike intact hyaluronic acid with a molecular weight of several megadaltons, generally showing distinctive antiangiogenic properties, intermediate fractions of hyaluronan hydrolysis in a range from 2.5 to 200 kilodaltons have a stimulating effect on angiogenesis. Intercellular contacts between platelets and endotheliocytes are stabilized due to adhesive transmembrane glycoprotein PECAM-1 interaction. Resulting PECAM-1 heterodimers acquire conformation with high affinity to integrins αvβ3. Integrin activation forms contact links between endothelium and fibrillar proteins. Activated endotheliocytes secrete von Willebrand factor and P-selectin. These proteins are accumulated in Weibel–Palade bodies. Vasopressin stimulates cAMP-dependent ACAP-regulated exocytosis of Weibel–Palade bodies. von Willebrand factor possesses adhesive properties and additionally accelerates interaction of cells with the intercellular matrix. Adhesion on fibrillar collagen and membrane glycoproteins in cooperation with effects of PECAM-1–αvβ3 integrin complexes fixes cell aggregates in the surrounding interstitium and promotes proliferating endotheliocyte migration in according to the direction of local growth factor gradients during angiogenesis. Neurohormonal regulation of platelet and endotheliocyte secretory activity functionally link proliferation and migration of endotheliocytes during angiogenesis and integrate it according to the adaptive capacity of the entire organism.

Staphylococcus aureus induces the expression of VCAM-1, P- and E-selectins on the endothelial cells of the EA.hy926 cell line but, at the same time, causes the significant suppression of the force and work of adhesion between these receptors of endotheliocytes and the receptors of neutrophils in an experimental septicemia model. Adhesion contacts between the receptors of neutrophils and endotheliocytes are statistically significantly suppressed under non-opsonized and opsonized S. aureus treatment, which disrupts the initial stage of transendothelial migration of neutrophils—adhesion. Thus, S. aureus causes the arrest of neutrophils in the bloodstream in an experimental septicemia model.

Proliferative effects of vasopressin belong to the least studied field of molecular biochemistry of peptide hormones. At the same time, synthetic preparations of vasopressin are widely used in the treatment of vascular diseases and in oncology. In a number of cases, vasopressin has proliferative effects; however, emerging information about the antiproliferative properties of the hormone is currently being more actively discussed. Any proliferation is accompanied by tissue neovascularization. Two main types of vasopressin receptors are expressed in the blood vessels. In this regard, analysis of how the vasopressin effect works with access to mitogenic and secretory effects in blood vessel cells is topical. The review considers tissue-specific peculiarities of vasopressin receptor expression and recent data concerning the organization of signal transduction of hormonal reception. Attention is focused on smooth muscle cells and platelets expressing V1А-type receptors and on endotheliocytes expressing V2 vasopressin receptors. The structure of glycopeptides and enzymes playing the role of mediators in noncanonical transduction of the hormonal signal was analyzed in detail. Particular attention was paid to the molecular organization of platelet/endothelial cell adhesion protein (PECAM-1). The integral glycopeptide PECAM-1 performs simultaneously structural and signaling functions, converting the vasoconstrictor effect of V1А vasopressin receptors into the reaction of other membrane receptors and intracellular enzymes of blood vessels. The cytoplasmic department of PECAM-1 is involved in the inhibition of VEGFR-2 receptor of vascular endothelial growth factor (VEGF), the main stimulator of endotheliocyte proliferation. Intercellular dimers of PECAM-1 activate integrins. The integrin αVβ3 and von Willebrand factor are expressed in endotheliocytes. Multimeric molecules of von Willebrand factor are involved in cooperation between the endothelium and interstitium with local reorganization of the vascular network accompanying the repair of blood vessels in trauma and tumor progression. The von Willebrand factor aggregates the complexes of ανβ3 integrins with other ligands and membrane receptors of endotheliocytes and platelets, fixing the cells to the basement membrane. V1А vasopressin receptors activate VEGF secretion in platelets and proliferation of myocytes. V2 receptors stimulate exocytosis of Weibel–Palade bodies and secretion of von Willebrand factor in endotheliocytes, inducing chemotaxis of smooth muscle cells and endotheliocytes. Activated ανβ3 integrins physically interact with VEGFR-2 receptors of endotheliocytes and modulate the stimulation of angiogenic effects. [ABSTRACT FROM AUTHOR]

We have developed a model for evaluating the integral intercellular interactions in the "endotheliocyte‐neutrophil" system and have shown the high variability of adhesion contacts in different donors associated with different expression profiles of neutrophils. Two methods (forсe spectroscopy‐spectroscopy and scanning ion‐conductance microscopy) showed a decrease in the rigidity of the membrane‐cytoskeletal complex of neutrophils under the influence of Staphylococcus aureus 2879 M. Adding this strain to the "endotheliocyte‐neutrophil" system caused a statistically significant decrease in the adhesion force and adhesion work, which indicates a change in the expression profile and physicochemical properties of membranes of both types of interacting cells (neutrophils and endotheliocytes). [ABSTRACT FROM AUTHOR]

Cytoplasmic actin structures are essential components of the eukaryotic cytoskeleton. According to the classic concepts, actin structures perform contractile and motor functions, ensuring the possibility of cell shape changes during cell spreading, polarization, and movement both in vitro and in vivo, from the early embryogenesis stages and throughout the life of a multicellular organism. Intracellular organization of actin structures, their biochemical composition, and dynamic properties play a key role in the realization of specific cellular and tissue functions and vary in different cell types. This paper is a review of recent studies on the organization and properties of actin structures in endotheliocytes, interaction of these structures with other cytoskeletal components and elements involved in cell adhesion, as well as their role in the functional activity of endothelial cells. [ABSTRACT FROM AUTHOR]

This article represents the electronic-microscopic examination of blood vessels of the hemomicrocirculatory bed of the iliac lymph nodes of white rats, males of reproductive age, who, during six weeks, received narcotic opioid analgesic – nalbuphine, increasing the weekly dose of the medicine to create a model of physical opioid dependence according to Ukraine Patent #76564 U. It was determined that opioid nalbuphine causes the reactive changes in the blood vessels of the hemomicrocirculatory bed of the iliac lymph nodes in the early stages of drug administration – within 1-2 weeks. A prolonged six-week administration of nalbuphine leads to profound destructive changes in the microvessels: the lumen of the hemocapillaries, which contains mainly the destructively altered erythrocytes, is expanding; the wall of microvessels, accompanied by hemorrhages into the vascular space, is violated; the structure of endotheliocytes nuclei changes, their cytoplasm swells, and organelles are damaged in it; the basement membrane thickens; the perivascular space swells and dilates. One week after the abolition of nalbuphine, the inverse changes in the blood vessels of hemomicrocirculatory bed do not occur.

Introduction Previous studies showed that homocysteine (Hcy) could injure vascular endothelial cells via several mechanisms, including its promotion of oxidative stress pathway and endoplasmic reticulum stress ( ER stress) pathway. Salidroside ( SAL) is an active component of Rhodiola rosea with documented antioxidative properties. Emerging evidence conformed that SAL attenuated Hcy-induced endothelial dysfunction by reducing oxidative stress. However, its role in ER stress pathway remains unclarified. Aims The purpose of this study was to explore the mechanism of the protective effect of SAL on Hcy-induced endothelial dysfunction. Results Pretreatment of the human umbilical vein endothelial cells ( HUVECs) with SAL significantly reduced the cell damage effects brought by Hcy in a dose-dependent manner. Functional studies on the HUVECs found that SAL rescued the endoplasmic reticulum stress induced by Hcy. The underlying mechanisms involve the inhibition of Hcy-induced activation of binding protein (Bip) and C/ EBP homologous protein ( CHOP), as well as the phosphorylation of protein kinase RNA-like ER kinase ( PERK) or inositol-requiring enzyme 1 alpha ( IRE1α). Conclusions Taken together, these findings implicate that SAL could regulate ER stress pathway on the viability of endotheliocyte induced by Hcy in vitro. Our findings provide the first evidence that SAL plays an important role in endotheliocyte protection via suppressing ER stress pathway in HUVEC cells and that it may be a promising therapeutic target for atherosclerosis and cardiovascular disease. [ABSTRACT FROM AUTHOR]

[Display omitted] The inflammatory response is the basis of many diseases, such as atherosclerosis and ulcerative colitis. Inhibiting inflammatory response is the key to treating these diseases. Berberine hydrochloride (BBR), a natural product, has shown effective inflammation inhibitory activity. However, its distribution throughout the body results in a variety of serious side effects. Currently, there is a lack of targeted delivery systems for BBR to inflammatory sites. In view of the fact that the recruitment of inflammatory cells by activated vascular endothelial cells is a key step in inflammation development. Here, we design a system that can specifically deliver berberine to activated vascular endothelial cells. Low molecular weight fucoidan (LMWF), which can specifically bind to P-selectin, was coupled to PEGylated liposomes (LMWF-Lip), and BBR is encapsulated into LMWF-Lip (LMWF-Lip/BBR). In vitro, LMWF-Lip significantly increases the uptake by activated human umbilical vein endothelial cells (HUVEC). Injection of LMWF-Lip into the tail vein of rats can effectively accumulate in the swollen part of the foot, where it is internalized by the characteristics of activated vascular endothelial cells. LMWF-Lip/BBR can effectively inhibit the expression of P-selectin in activated vascular endothelial cells, and reduce the degree of foot edema and inflammatory response. In addition, compared with free BBR, the toxicity of BBR in LMWF-Lip/BBR to main organs was significantly reduced. These results suggest that wrapping BBR in LMWF-Lip can improve efficacy and reduce its systemic toxicity as a potential treatment for various diseases caused by inflammatory responses. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the protective effect of propyl gallate (PG), an alkyl ester of gallic acid which is an active ingredient of Radix Paeoniae, against oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and death in endothelial cells (ECs) and to find out its preliminary mechanism. Methods: The cultured endothelial cells were divided into normal, model (ox-LDL), control (fetal bovine serum), PG high dose (20 μg/mL), PG middle dose (10 μg/mL), and PG low dose (5 μg/mL) groups, each derived from three different pools of umbilical cords. The model of injured human umbilical vein endothelial cells (HUVECs) was induced by ox-LDL. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst 33258 staining, flow cytometry and measurement of nitrogen monoxidum (NO) release were used to evaluate the protective effect of PG against ox-LDL-induced apoptosis and death in HUVECs. To find out the mechanism of this protective effect, the expression of endothelial nitric oxide synthase (eNOS) mRNA, eNOS protein expression, immunofluorescence of intracellular reactive oxygen species (ROS) and activities of malondialdehyde (MDA), superoxidedismutase (SOD) and glutathione peroxidase (GPx) were observed. Results: PG significantly reduced ox-LDL-induced apoptosis and cell death. The percentage of cells death and apoptosis was significantly higher in the ox-LDL group than that in the control group ( P<0.05). Compared with the control group, the cells death and apoptosis of PG group was no different ( P>0.05). As compared with the ox-LDL group, results of the PG high dose group showed that cell viability was significantly increased ( P<0.05), the level of NO release, expression of eNOS mRNA, densitometric value of eNOS protein expression, as well as the activities of SOD and GPx were all significantly higher (all P<0.05). Conclusion: PG could potentially serve as a novel endothelial protective agent against ox-LDL-induced injury of endothelial cell. [ABSTRACT FROM AUTHOR]

Abstract: Background: Low success rate of blood glucose in diabetes is an international problem. The endothelia cytotoxicity of hyperglycemia has been widely accepted. However, it has not been seen in reports of the value of concentration of high glucose beginning to produce cytotoxicity and the relationship between hyperglycemia and cytotoxicity as well as how to effectively prevent and control hyperglycemia cytotoxicity. Dan Gua prescription is an effective Chinese herb prescription for diabetic vascular complications. Methods: Dan Gua prescription was contained in Dan Gua liquor utilized in experiments. (1) The cytotoxicity experiment of Dan Gua was carried out with M199 medium whose glucose (Glu) was 5.55 mmol/l to seek for a suitable experimental concentration of Dan Gua. (2) The human vessel endotheliocyte was cultivated for 72 h with mediums containing glucose in different concentrations (Group G1 to Group G11, Glu: 5.5 to 99.9 mmol/l, respectively), and assayed an optical density (OD) value using the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide method. (3) Experiment 2 was repeated. However, the medium of each group (Groups Y1 to Y11) contained Dan Gua liquor whose concentration was 1/300. Results: There was a negative correlation between means of cell OD values and glucose concentrations (r=−.927, R 2=.844), and it presented a notable linear correlation (y=0.681−0.002x). Based on the OD value of 5.5-mmol/l glucose concentration (group G1), when glucose concentration reached 22.2 mmol/l (G4), the difference in OD values has a statistical significance. OD values in Y1–Y11 were not less than that of G1. Conclusion: There is a notable linear correlation between the endothelial cytotoxicities of Glu and its concentrations. The spinodal point concentration of statistical significance of hyperglycemia cytotoxicity is 22.2 mmol/l; 1/300 Dan Gua can reverse the endothelia cytotoxicity in different concentrations of hyperglycemia. [Copyright &y& Elsevier]

Objective: The aim: To study morphometric and electron microscopic changes in the parenchyma of rat lymph nodes under the action of sodium glutamate and its correction by orlistat., Patients and Methods: Materials and methods: The article presents and analyzes the data of an experimental study conducted on 66 white male rats and females of reproductive age. Experimental animals are divided into 4 groups., Results: Results: After six weeks of exposure to monosodium glutamate, there was a significant decrease in the relative area of the cortical substance in the lymph nodes of white male and female rats by 11.95% and 9.31% and, respectively, an increase in the relative area of the medullary substance by 18.76% and 14.7% in compared with an intact group of animals. After six weeks of sodium glutamate and the next six weeks of the standard diet of vivarium and orlistat, the relative area of the cortical substance in the lymph node parenchyma was 2.55% and 0.38% more than the parameters of the intact group of animals, respectively. Accordingly, the relative area of the medullary substance decreased and was 4.01% and 0.59% less compared to the intact group of animals., Conclusion: Conclusions: Electron microscopic examination showed that monosodium glutamate causes changes in the parenchyma of the lymph nodes as in a high-calorie diet. The introduction of orlistat (xenical) leads to a partial restoration of the structural organization, and hence the function of this organ.

Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo , thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs. Several mechanisms have been described to control ageing-related endothelial cell senescence including microRNAs, mitochondrial dysfunction and micro environmental stressors, such as hypoxia. In this review, we attempt to summarize the recent literature in the field, discussing the major mechanisms involved in endothelial cell senescence. We also underline key molecular aspects of ageing-associated vascular dysfunction in the attempt to highlight potential innovative therapeutic targets to delay the onset of age-related diseases., (Copyright © 2016. Published by Elsevier Ireland Ltd.)