The role of cytoskeleton in the regulation of vascular endothelial barrier function

Bogatcheva, Natalia V.; Verin, Alexander D.

doi:10.1016/j.mvr.2008.06.003

Cited by 167 publications

(155 citation statements)

References 66 publications

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“…A number of cellular pathways are known to regulate cell adhesion in endothelial cells. These include growth factors, Rho GTPases, protein kinases and calcium signaling (34,35). The alteration of these pathways or of adhesion molecules may trigger the radiation-induced retraction observed by others in endothelial cells (13,14).…”

Section: Effects Of High Let Irradiation On the Cell Cyclementioning

confidence: 99%

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Beck

Rombouts

Moreels

et al. 2014

International Journal of Molecular Medicine

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Abstract. Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/ µm) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by γ-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-κB, may be involved in these cellular responses.

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Section: Effects Of High Let Irradiation On the Cell Cyclementioning

confidence: 99%

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Beck

Rombouts

Moreels

et al. 2014

International Journal of Molecular Medicine

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show abstract

“…d. HUVEC plated as described above were assayed for apoptosis by flow cytometry using an Annexin-V/PI assay kit VE-cadherin is linked to the actin-myosin cytoskeleton via b-catenin. The cytoskeleton plays a central role in the regulation of endothelial permeability and cell migration by controlling cell shape [4,30]. Activation of the endothelial contractile machinery and generation of contractile forces by endothelial cells can cause adjacent cells to retract from each other.…”

Section: Effects Of Tr-644 On Microtubules and Actin Microfilament Inmentioning

confidence: 99%

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

et al. 2013

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TR-644 is a novel combretastatin A-4 (CA-4) analogue endowed with potent microtubule depolymerizing activity superior to that of the lead compound and it also has high affinity to colchicines binding site of tubulin. We tested TR-644 anti-angiogenic effects in human umbilical endothelial cells (HUVEC). It showed no significant effects on the growth of HUVEC cells at concentrations below 1,000 nM, but at much lower concentrations (10-100 nM) it induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the disruption of the microtubule network. TR-644 also increased permeability of HUVEC cells in a time dependent manner. The molecular mechanism for the anti-vascular activity of TR-644 was investigated in detail. TR-644 caused G2/M arrest in endothelial cells and this effect correlated with downregulation of the expression of Cdc25C and Cdc2Tyr15 .Moreover TR-644 inhibited VEGF-induced phosphorylation of VE-cadherin but did not prevent the VEGF-induced phosphorylation of FAK. In chick chorioallantoic membrane in vivo assay, TR-644 (0.1-1.0 pmol/egg) efficiently counteracted the strong angiogenic response induced by FGF. Also CA-4, used as reference compound, caused an antagonistic effect, but in contrast, it induced per se, a remarkable angiogenic response probably due to an inflammatory reaction in the site of treatment. In a mice allogenic tumor model, immunohistochemical staining of tumors with anti-CD31 antibody showed that TR-644 significantly reduced the number of vessel, after 24 h from the administration of a single dose (30 mg/Kg).

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“…The vascular endothelial cadherin (VE-cadherin) represents one of the major adhesion systems that support the endothelial barrier function. Signalling pathways that increase vascular permeability generally affect adhesive function of VE-cadherin, in part, through tyrosine phosphorylation of constituents of adherens junctions and activation of acto-myosin contractibility accompanied by reorganization of the actin cytoskeleton that cause formation of stress fibrer and intercellular gaps 8,12 .…”

mentioning

confidence: 99%

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

et al. 2015

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Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.

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The role of cytoskeleton in the regulation of vascular endothelial barrier function

Cited by 167 publications

References 66 publications

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

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