Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4130-4137 ◽  
Author(s):  
Jinmin Gao ◽  
Lei Sun ◽  
Lihong Huo ◽  
Min Liu ◽  
Dengwen Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

scholarly journals Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension

2016 ◽  
Vol 310 (3) ◽  
pp. L249-L262 ◽  
Author(s):  
Andrew J. Bryant ◽  
Ryan P. Carrick ◽  
Melinda E. McConaha ◽  
Brittany R. Jones ◽  
Sheila D. Shay ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Endothelial Cell ◽  
Pulmonary Fibrosis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Pulmonary Vessel ◽  
Deficient Mice

Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.

scholarly journals miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2

2020 ◽  
Vol 52 (2) ◽  
pp. 180-191 ◽  
Author(s):  
Qiaoli Chen ◽  
Xiaoye Li ◽  
Lingjun Kong ◽  
Qing Xu ◽  
Zi Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Nuclear Factor Κb ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Cell Dysfunction ◽  
Umbilical Vein Endothelial Cells

Abstract Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.

scholarly journals Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Changyou Li ◽  
Siyuan Li ◽  
Changkai Jia ◽  
Lingling Yang ◽  
Zicheng Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Low Concentration ◽  
Huvec Cells

Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC) line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenicEscherichia coliinfection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.

scholarly journals Divergent effects of extracellular and intracellular alkalosis on Ca2+ entry pathways in vascular endothelial cells

1997 ◽  
Vol 323 (2) ◽  
pp. 567-573 ◽  
Author(s):  
Ichiro WAKABAYASHI ◽  
Klaus GROSCHNER
Keyword(s):  
Endothelial Cells ◽  
Membrane Potential ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Free Solution ◽  
Store Depletion ◽  
Acute Elevation ◽  
Stimulation Of

Modulation by alkalosis of basal leak Ca2+ entry and store-depletion-induced Ca2+ entry was investigated in the vascular endothelial cell line ECV 304. Ca2+ entry was monitored as the increase in the intracellular free Ca2+ concentration ([Ca2+]i) induced by elevation of the extracellular Ca2+ concentration. When ECV 304 cells were challenged with 100 nM thapsigargin in nominally Ca2+-free solution, [Ca2+]i increased transiently, and the increase in [Ca2+]i during a subsequent cumulative elevation of extracellular Ca2+ (from nominally Ca2+-free up to 5 mM) was markedly enhanced compared with non-stimulated cells (i.e. basal Ca2+ leak). Prolonged elevation of the extracellular pH (pHo) from 7.4 to 7.9 did not affect resting [Ca2+]i or the thapsigargin-induced [Ca2+]i transient evoked in nominally Ca2+-free solution, but increased leak Ca2+ entry as well as store-depletion-activated Ca2+ entry significantly. Basal Ca2+ leak and store-depletion-activated Ca2+ entry were enhanced either by acute elevation of pHo from 7.4 to 7.9 or by chronic alkalosis (pHo = 7.9). Stimulation of Ca2+ entry by extracellular alkalosis was observed both in normal and in high extracellular K+ (110 mM) solution, suggesting that the effects of alkalosis are independent of membrane potential. The intracellular pH (pHi) increased slightly during both acute and chronic extracellular alkalosis (from 7.22±0.01 to 7.37±0.04 and 7.45±0.05 respectively). Elevation of pHi to 7.60±0.06 at constant pHo by administration of 20 mM NH4Cl failed to stimulate, and in fact inhibited, store-depletion-activated Ca2+ entry. Our results demonstrate that a decrease in the extracellular but not the intracellular proton concentration promotes both basal and stimulated Ca2+ entry into endothelial cells.

scholarly journals Exogenous H2S Regulates of Cystathionine Gamma-Lyase in HUVECs During Hypoxia

2020 ◽  
Author(s):  
Maoxian Wang
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Mrna Expression ◽  
Blood Vessels ◽  
Western Blotting ◽  
Promoter Activity ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Luciferase Assay ◽  
Vascular Endothelial

Cystathionine gamma-lyase (CSE) is one of the essential H2S-producing enzymes, and it regulates diverse functions in connection with cardiovascular function. It is crucial how exogenous H2S regulates CSE expression of the vascular endothelial cell during hypoxia. We examined the transcription and expression of CSE in HUVECs regulated by exogenous H2S with 100 μM during hypoxia by Luciferase assay, Western blotting, and quantitative RT-qPCR. Exogenous H2S influenced on the promoter activity of CSE in HUVECs during hypoxia. The effects of 100 μM H2S on CSE mRNA expression in HUVECs is decreased compared with 0 μM H2S. The consequences of 100 μM H2S on the expression level of CSE protein in HUVECs at two h of hypoxia is reduced compared with 0 μM H2S. These findings suggest that vascular endothelial cells can respond to the signals of hypoxia in the blood, and can respond to changes in H2S concentration in the blood, thus affect the blood vessels themselves.

Vascular endothelial cell lineage-specific promoter in transgenic mice

Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1089-1098 ◽  
Author(s):  
T.M. Schlaeger ◽  
Y. Qin ◽  
Y. Fujiwara ◽  
J. Magram ◽  
T.N. Sato
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Es Cells ◽  
Vascular Endothelial Cell ◽  
Cell Lineage ◽  
Vascular Endothelial ◽  
Lacz Reporter

Vascular endothelial cells play essential roles in the function and development of the cardiovascular system. However, due to the lack of lineage-specific markers suitable for molecular and biochemical analyses, very little is known about the molecular mechanisms that regulate endothelial cell differentiation. We report the first vascular endothelial cell lineage-specific (including angioblastic precursor cells) 1.2 kb promoter in transgenic mice. Moreover, deletion analysis of this promoter region in transgenic embryos revealed multiple elements that are required for the maximum endothelial cell lineage-specific expression. This is a powerful molecular tool that will enable us to identify factors and cellular signals essential for the establishment of vascular endothelial cell lineage. It will also allow us to deliver genes specifically into this cell type in vivo to test specifically molecules that have been implicated in cardiovascular development. Furthermore, we have established embryonic stem (ES) cells from the blastocysts of the transgenic mouse that carry the 1.2 kb promoter-LacZ reporter transgene. These ES cells were able to differentiate in vitro to form cystic embryoid bodies (CEB) that contain endothelial cells determined by PECAM immunohistochemistry. However, these in vitro differentiated endothelial cells did not express the LacZ reporter gene. This indicates the lack of factors and/or cellular interactions which are required to induce the expression of the reporter gene mediated by this 1.2 kb promoter in this in vitro differentiation system. Thus this system will allow us to screen for the putative inducers that exist in vivo but not in vitro. These putative inducers are presumably important for in vivo differentiation of vascular endothelial cells.

Role of protein kinase C β2 activation in TNF-α-induced human vascular endothelial cell apoptosis

2009 ◽  
Vol 87 (3) ◽  
pp. 221-229 ◽  
Author(s):  
Fang Wang ◽  
Hui-min Liu ◽  
Michael G. Irwin ◽  
Zhong-yuan Xia ◽  
Zhiyong Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Human Vascular Endothelial Cell ◽  
Kinase C ◽  
Tnf Α

The circulatory inflammatory cytokine tumor necrosis factor alpha (TNF-α) is increased in pathologic conditions that initiate or exacerbate vascular endothelial injury, such as diabetes. Protein kinase C (PKC) has been shown to play a critical role in TNF-α-induced human endothelial cell apoptosis. However, the relative roles played by specific isoforms of PKC in TNF-α-induced human endothelial cell apoptosis have not been addressed. We investigated the effects of a selective PKCβ2 inhibitor (CGP53353) on TNF-α-induced apoptosis in human vascular endothelial cells (cell line ECV304) and on the production of reactive oxygen species and nitric oxide, and compared its effects with rottlerin, a reagent that has been shown to reduce PKCδ protein levels. Cultured human vascular endothelial cells (ECV304) were treated for 24 h with one of 4 regimes: 40 ng/mL TNF-α alone (TNF-α), TNF-α with 10 µmol/L rottlerin (T+rottlerin), TNF-α with 1 µmol/L CGP53353 (T+CGP), or untreated (control). Cell viability was measured by MTT assay, and cell apoptosis was assessed by flow cytometry. TNF-α-induced endothelial cell apoptosis was associated with dramatic increases in production of intracellular hydrogen peroxide (approximately 20 times greater than control) and superoxide (approximately 16 times greater than control), as measured by dichlorofluorescein and dihydroethidium fluorescent staining, respectively. This increase was accompanied by reduced activity of superoxide dismutase and glutathione peroxidase and, subsequently, an increase in the lipid peroxidation product malondialdehyde. CGP53353, but not rottlerin, abolished or attenuated all these changes. We conclude that PKCβ2 plays a major role in TNF-α-induced human vascular endothelial cell apoptosis.

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