Effects of Flow Patterns on the Localization and Expression of VE-Cadherin at Vascular Endothelial Cell Junctions: In vivo and in vitro Investigations

2005 ◽  
Vol 42 (1) ◽  
pp. 77-89 ◽  
Author(s):  
Hui Miao ◽  
Ying-Li Hu ◽  
Yan-Ting Shiu ◽  
Suli Yuan ◽  
Yihua Zhao ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Flow Patterns ◽  
Cell Junctions ◽  
Vascular Endothelial

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 LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6

2021 ◽  
Vol 9 ◽  
Author(s):  
Huihua Kai ◽  
Qiyong Wu ◽  
Ruohan Yin ◽  
Xiaoqiang Tang ◽  
Haifeng Shi ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Thoracic Aorta ◽  
Gene Transcription ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury ◽  
Atherosclerosis Development

Coronary artery disease (CAD) is a major atherosclerotic cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of lncRNA non-coding RNA activated by DNA damage (NORAD) on atherosclerosis in CAD remains unclear. The primary aim of this study was to investigate the effect of lncRNA NORAD on vascular endothelial cell injury and atherosclerosis. Here, ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE–/– mice were utilized as in vitro and in vivo models. The present study found that lncRNA NORAD expression was increased in ox-LDL-treated HUVECs and thoracic aorta of atherosclerotic mice, and knockdown of lncRNA NORAD alleviated vascular endothelial cell injury and atherosclerosis development in vitro and in vivo. Knockdown of lncRNA NORAD aggravated ox-LDL-reduced or atherosclerosis-decreased vascular endothelial growth factor (VEGF) expression in HUVECs and thoracic aorta of mice to ameliorate vascular endothelial cell injury and atherosclerosis development. Moreover, nucleus lncRNA NORAD suppressed VEGF gene transcription through enhancing H3K9 deacetylation via recruiting HDAC6 to the VEGF gene promoter in ox-LDL-treated HUVECs. In addition, VEGF reduced FUS (FUS RNA binding protein) expression by a negative feedback regulation in HUVECs. In summary, lncRNA NORAD enhanced vascular endothelial cell injury and atherosclerosis through suppressing VEGF gene transcription via enhancing H3K9 deacetylation by recruiting HDAC6. The findings could facilitate discovering novel diagnostic markers and therapeutic targets for CAD.

Multi-omics analysis reveals size-dependent toxicity and vascular endothelial cell injury induced by microplastic exposure in vivo and in vitro

2022 ◽  
Author(s):  
min zhang ◽  
jun shi ◽  
qiong huang ◽  
yi xie ◽  
ruihao wu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Vascular System ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury ◽  
Size Dependent ◽  
Exposure In Vivo

Microplastics (MPs) pollution has gained increasing attention recently. Fewer studies have examined the effects of these small items on the vascular system. The aim of this work was to precisely...

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.

VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs

2014 ◽  
Vol 307 (3) ◽  
pp. H455-H463 ◽  
Author(s):  
Adama Sidibé ◽  
Helena Polena ◽  
Karin Pernet-Gallay ◽  
Jeremy Razanajatovo ◽  
Tiphaine Mannic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Reproductive Tract ◽  
Cell Junctions ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 ± 0.3, n = 78; and VE-Y685F, 12.48 ± 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary permeability. Furthermore, this knock-in mouse model is of potential interest for further studies of diseases that are associated with abnormal vascular permeability.

scholarly journals MEF2A Is the Trigger of Resveratrol Exerting Protection on Vascular Endothelial Cell

2022 ◽  
Vol 8 ◽  
Author(s):  
Benrong Liu ◽  
Lihua Pang ◽  
Yang Ji ◽  
Lei Fang ◽  
Chao Wei Tian ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Atherosclerotic Lesion ◽  
Vascular Endothelial ◽  
Experimental Conditions ◽  
Protective Function

Both resveratrol and myocyte enhancer factor 2A (MEF2A) may protect vascular endothelial cell (VEC) through activating the expression of SIRT1. However, the relationship between resveratrol and MEF2A is unclear. We aimed to investigate the deeper mechanism of resveratrol in protecting vascular endothelial cells and whether MEF2A plays a key role in the protective function of resveratrol. Human umbilical vein endothelial cell (HUVEC) was used for in vitro study, and small interfere RNA was used for silencing MEF2A. Silencing MEF2A in the vascular endothelium (VE) of ApoE−/− mice was performed by tail injection with adeno associated virus expressing si-mef2a-shRNA. The results showed that treatment of HUVEC with resveratrol significantly up-regulated MEF2A, and prevented H2O2-induced but not siRNA-induced down-regulation of MEF2A. Under various experimental conditions, the expression of SIRT1 changed with the level of MEF2A. Resveratrol could rescue from cell apoptosis, reduction of cell proliferation and viability induced by H2O2, but could not prevent against that caused by silencing MEF2A with siRNA. Silencing MEF2A in VE of apoE−/− mice decreased the expression of SIRT1, increased the plasma LDL-c, and abrogated the function of resveratrol on reducing triglyceride. Impaired integrity of VE and aggravated atherosclerotic lesion were observed in MEF2A silenced mice through immunofluorescence and oil red O staining, respectively. In conclusion, resveratrol enhances MEF2A expression, and the upregulation of MEF2A is required for the endothelial protective benefits of resveratrol in vitro via activating SIRT1. Our work has also explored the in vivo relevance of this signaling pathway in experimental models of atherosclerosis and lipid dysregulation, setting the stage for more comprehensive phenotyping in vivo and further defining the molecular mechanisms.

scholarly journals Fibrin Regulation of Interleukin-8 Gene Expression in Human Vascular Endothelial Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3595-3602 ◽  
Author(s):  
Jiafan Qi ◽  
Sandra Goralnick ◽  
Donald L. Kreutzer
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Chemotactic Factor ◽  
Interleukin 8 ◽  
Leukocyte Recruitment ◽  
Vascular Endothelial

Abstract Recent studies in our laboratory, as well as others, have suggested that fibrin can regulate cell function in vitro and likely control inflammation in vivo by acting as a potent cell activator. This has led us to hypothesize that during tissue and vascular injury, fibrin can enhance leukocyte recruitment by inducing vascular endothelial cell expression of leukocyte chemotactic factors. To begin to test this hypothesis, we developed an in vitro model of in situ fibrin polymerization on human umbilical vein endothelial cell culture (HUVEC) and determined the ability of fibrin to induce HUVEC expression of the potent leukocyte chemotactic factor interleukin-8 (IL-8). Our initial studies showed that fibrin induced IL-8 expression in a time- and dose-dependent fashion. Fibrin-induced IL-8 expression in HUVEC could be seen as early as 2 hours post-fibrin stimulation. Additionally, fibrin concentrations as low as 30 μg/mL stimulated a detectable level of IL-8 antigen expression from HUVEC. We also showed that this fibrin induced IL-8 had the identical molecular weight and similar antigenic identity as recombinant and monocyte derived IL-8. Northern blot analysis showed that the IL-8 antigen increase seen in fibrin treated HUVEC was due to fibrin induced elevation of steady state mRNA expression in HUVEC. These data clearly support our hypothesis that fibrin is a potent vascular endothelial cell (VEC) activator that can directly contribute to leukocyte recruitment and activation by inducing leukocyte chemotactic factor expression from VEC.

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