Fibrinogen alters mouse brain endothelial cell layer integrity affecting vascular endothelial cadherin

Nanomaterial induced endothelial cells leakiness (NanoEL) is caused because nanomaterials enter the interstitial space of endothelial cells and disrupt the endothelial cell-cell interactions by interacting with vascular endothelial cadherin (VE-cad)....

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ACTH depletion represses vascular endothelial-cadherin transcription in mouse adrenal endothelium in vivo

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01641 ◽

2005 ◽

Vol 34 (1) ◽

pp. 127-137 ◽

Cited By ~ 7

Author(s):

Philippe Huber ◽

Christine Mallet ◽

Elodie Faure ◽

Christine Rampon ◽

Marie-Hélène Prandini ◽

...

Keyword(s):

Endothelial Cell ◽

Vascular Endothelial ◽

Flow Cytometry Analysis ◽

Adhesion Protein ◽

Adrenal Cells ◽

Protein Levels ◽

Vascular Endothelial Cadherin ◽

Complex Architecture

Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion protein that is localised at cell–cell contacts. This molecule is an important determinant of vascular architecture and endothelial cell survival. In the adrenal cortex, steroidogenic and endothelial cells form a complex architecture. The adrenocorticotrophin hormone (ACTH) regulates gland homeostasis whose secretion is subjected to a negative feedback by adrenocorticosteroids. The aim of the present study was to determine whether VE-cadherin expression in the adrenal gland was regulated by hormonal challenge. We demonstrated that VE-cadherin protein levels were dramatically decreased (23.5 ± 3.7%) by dexamethasone injections in the mouse and were restored by ACTH within 7 days (94.9 ± 18.6%). Flow cytometry analysis of adrenal cells showed that the ratios of endothelial versus total adrenal cells were identical (35%) in dexamethasone- or ACTH-treated or untreated mice, suggesting that VE-cadherin expression could be regulated by ACTH. We demonstrate the existence of a transcriptional regulation of the VE-cadherin gene using transgenic mice carrying the chloramphenicol acetyl transferase gene under the control of the VE-cadherin promoter. Indeed, the promoter activity in the adrenals, but not in the lung or liver, was decreased in response to dexamethasone treatment (40 ± 1.3%) and was partially restored after gland regeneration by ACTH injection (82 ± 3%). In conclusion, our results show that transcription of a specific endothelial gene is controlled by the hypothalamo–pituitary axis and the data expand the knowledge regarding the role of ACTH in the regulation of the adrenal vascular network.

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Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia

Stroke ◽

10.1161/strokeaha.119.025304 ◽

2020 ◽

Vol 51 (9) ◽

pp. 2844-2853 ◽

Cited By ~ 1

Author(s):

Su Jing Chan ◽

Elga Esposito ◽

Kazuhide Hayakawa ◽

Emiri Mandaville ◽

Raymond A.A. Smith ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cell ◽

Growth Factor ◽

Blood Brain Barrier ◽

Neural Progenitor Cells ◽

Brain Barrier ◽

Vascular Endothelial ◽

Brain Endothelial Cell ◽

Blood Brain ◽

Endothelial Growth Factor

Background and Purpose: Although VEGF 165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF 165 -binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. Methods: Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. Results: HS7 significantly enhanced VEGF 165 -mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. Conclusions: A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF 165 activity during the post-ischemic recovery phase of stroke.

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Role of kinase-independent and -dependent functions of FAK in endothelial cell survival and barrier function during embryonic development

The Journal of Cell Biology ◽

10.1083/jcb.200912094 ◽

2010 ◽

Vol 189 (6) ◽

pp. 955-965 ◽

Cited By ~ 76

Author(s):

Xiaofeng Zhao ◽

Xu Peng ◽

Shaogang Sun ◽

Ann Y.J. Park ◽

Jun-Lin Guan

Keyword(s):

Endothelial Cell ◽

Normal Development ◽

Vascular Development ◽

Vascular Endothelial ◽

Vascular Endothelial Cadherin ◽

Abnormal Distribution ◽

Endothelial Cell Survival ◽

Independent Functions

Focal adhesion kinase (FAK) is essential for vascular development as endothelial cell (EC)–specific knockout of FAK (conditional FAK knockout [CFKO] mice) leads to embryonic lethality. In this study, we report the differential kinase-independent and -dependent functions of FAK in vascular development by creating and analyzing an EC-specific FAK kinase-defective (KD) mutant knockin (conditional FAK knockin [CFKI]) mouse model. CFKI embryos showed apparently normal development through embryonic day (E) 13.5, whereas the majority of CFKO embryos died at the same stage. Expression of KD FAK reversed increased EC apoptosis observed with FAK deletion in embryos and in vitro through suppression of up-regulated p21. However, vessel dilation and defective angiogenesis of CFKO embryos were not rescued in CFKI embryos. ECs without FAK or expressing KD FAK showed increased permeability, abnormal distribution of vascular endothelial cadherin (VE-cadherin), and reduced VE-cadherin Y658 phosphorylation. Together, our data suggest that kinase-independent functions of FAK can support EC survival in vascular development through E13.5 but are insufficient for maintaining EC function to allow for completion of embryogenesis.

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Endothelial Cell Layer Subjected to Impinging Flow Mimicking the Apex of an Arterial Bifurcation

Annals of Biomedical Engineering ◽

10.1007/s10439-008-9540-x ◽

2008 ◽

Vol 36 (10) ◽

pp. 1681-1689 ◽

Cited By ~ 59

Author(s):

Michael P. Szymanski ◽

Eleni Metaxa ◽

Hui Meng ◽

John Kolega

Keyword(s):

Endothelial Cell ◽

Cell Layer ◽

Arterial Bifurcation ◽

Endothelial Cell Layer ◽

Impinging Flow

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Albumin-derived advanced glycation end-products trigger the disruption of the vascular endothelial cadherin complex in cultured human and murine endothelial cells

Biochemical Journal ◽

10.1042/bj3590567 ◽

2001 ◽

Vol 359 (3) ◽

pp. 567-574 ◽

Cited By ~ 23

Author(s):

Karel OTERO ◽

Fernando MARTÍNEZ ◽

Amada BELTRÁN ◽

Deyarina GONZÁLEZ ◽

Beatriz HERRERA ◽

...

Keyword(s):

Endothelial Cell ◽

Advanced Glycation End Products ◽

Biological Effects ◽

Vascular Complications ◽

Vascular Endothelial ◽

Advanced Glycation ◽

Cell Extracts ◽

Vascular Endothelial Cadherin ◽

Glycation End Products ◽

End Products

Endothelial cell (EC) junctions regulate in large part the integrity and barrier function of the vascular endothelium. Advanced glycation end-products (AGEs), the irreversibly formed reactive derivatives of non-enzymic glucose–protein condensation reactions, are strongly implicated in endothelial dysfunction that distinguishes diabetes- and aging-associated vascular complications. The aim of the present study was to determine whether AGEs affect EC lateral junction proteins, with particular regard to the vascular endothelial cadherin (VE-cadherin) complex. Our results indicate that AGE-modified BSA (AGE-BSA), a prototype of advanced glycated proteins, disrupts the VE-cadherin complex when administered to ECs. AGE-BSA, but not unmodified BSA, was found to induce decreases in the levels of VE-cadherin, β-catenin and γ-catenin in the complex and in total cell extracts, as well as a marked reduction in the amount of VE-cadherin present at the cell surface. In contrast, the level of platelet endothelial cell adhesion molecule-1 (PECAM-1), which is located at lateral junctions, was not altered. Supplementation of the cellular antioxidative defences abolished these effects. Finally, the loss of components of the VE-cadherin complex was correlated with increases in vascular permeability and in EC migration. These findings suggest that some of the AGE-induced biological effects on the endothelium could be mediated, at least in part, by the weakening of intercellular contacts caused by decreases in the amount of VE-cadherin present.

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