Prolonged hypoxia alters endothelial barrier function

Ali, Mir H.; Schlidt, Scott A.; Hynes, Karen L.; Marcus, Benjamin C.; Gewertz, Bruce L.

doi:10.1067/msy.1998.89356

Cited by 7 publications

(9 citation statements)

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“…This has been suggested by measurements of oxygen tension in isolated Brockman bodies of fish [166] and in in vitro studies showing that islet function becomes impaired under prevailing low oxygen concentrations [167,168]. Furthermore, endothelial cell function is also adversely affected by hypoxia [169], which could lead to a disturbance of graft blood flow. Measurements with Clark type oxygen microelectrodes with a guard cathode [157] (outer tip diameter of 5-6 µm, and an inner tip diameter of 2 µm) have found that transplanted islets are hypoxic (7-10 mm Hg; 15% of normal partial pressure for oxygen), irrespective of implantation site (kidney, spleen, liver), without any improvement with time, for up to one year after transplantation [64,157].…”

Section: Lymphatic Capillaries and Capillary Blood Pressurementioning

confidence: 95%

Graft vascular function after transplantation of pancreatic islets

2002

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Endogenous pancreatic islets have a dense glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen and nutrients to the islet cells, provides signals from other cells in the body and disposes secreted hormones. Transplantation of isolated islets means that their vascular connection is interrupted. The islet grafts therefore depend upon endothelial cells and microvessels originating in the implantation organ for derivation of a new vascular system. A re-establishment of islet blood-flow occurs within 7-14 days after transplantation, mainly through vascular sprouting. The newly formed blood vessels acquire the morphological characteristics of those in endogenous islets. In intraportally transplanted islets to the liver, the islets become revascularized almost exclusively from tributaries to the hepatic artery. Exocrine contamination of the transplanted islets could hamper the revascularization process, whereas neither cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and RS-61443 have any essential effects on the angiogenesis. Investigators have noticed improvements in islet graft survival and function by means of basic fibroblast growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of the grafts. The functional properties of transplanted islets are largely unknown, but evidence from experimental islet transplantation suggests that both the blood perfusion and the tissue oxygen tension of the grafted islets are chronically decreased, indicating an insufficient vascular system. In order to achieve optimal condition for survival and function of transplanted beta cells, it is important to ascertain whether impairments in vascular function are present also after clinical islet transplantations as well.

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Section: Lymphatic Capillaries and Capillary Blood Pressurementioning

confidence: 95%

Graft vascular function after transplantation of pancreatic islets

2002

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“…Hypoxia-induced processes could also compromise the integrity of the vascular endothelium [35], resulting in an inability to function as an effective barrier to tumour cells. This might be one of the first steps towards intravasation, increasing the likelihood of metastatic formation.…”

Section: Discussionmentioning

confidence: 99%

“…This might be one of the first steps towards intravasation, increasing the likelihood of metastatic formation. Ali et al [35] demonstrated that severe hypoxia produced a significant reversible alteration in endothelial permeability, presumably as a result of a disruption of the tight junctions between endothelial cells, as well as the production and secretion of proteases and, for example, the vascular permeability factor (VPF/VEGF).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Tumour Cell Migration in an in vivo Chicken Model

et al. 2000

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To investigate the relationship between hypoxia, neovascularisation and tumour cell spread, experiments on the area vasculosa of the early chick embryo under different oxygen concentrations were performed in vivo. Human glioblastoma cells (U-138MG) were inoculated onto the area vasculosa and the fertilised eggs were incubated under conditions of normoxia or hypoxia. For evaluation, we performed in vivo video-microscopy of the area vasculosa and determination of microvessel density (MVD), as well as a histological examination of the fixed specimen. Under hypoxia, MVD was significantly increased compared to normoxic conditions. Only under hypoxic conditions was tumour cell spread found outside the main tumour mass and within the vessels, at times followed by the subsequent development of secondary tumour cell bulks on the area vasculosa. These data lead to the conclusion that hypoxia can stimulate tumour cell migration in this in vivo model.

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“…It is well documented that hypoxia is capable of reducing endothelial barrier function both in vivo and in vitro [24][25][26]. Therefore, our first objective was to determine if hypoxia also induced barrier dysfunction in VE monolayers.…”

Section: Barrier Dysfunction Is Accompanied By Upregulation Of Both Mmentioning

confidence: 99%

Involvement of HIF-1α in MLCK-dependent Endothelial Barrier Dysfunction in Hypoxia

Qi¹,

Wang²,

Liu³

et al. 2011

Cell Physiol Biochem

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The mechanisms of endothelial barrier dysfunction induced by hypoxia are incompletely understood. Hypoxia-inducible factor-1 alpha (HIF-1α) is a key transcription factor partially responsible for hypoxia-related responses, but its role in regulation of hypoxia-induced endothelial barrier dysfunction is unclear. The aim of this study was to determine the molecular mechanism by which HIF-1α regulates endothelial barrier function during hypoxia. Endothelial cell monolayers exposed to normoxia or hypoxia were used for physiological, morphological, and biochemical analyses. The results showed that hypoxia disrupts endothelial barrier function by upregulating protein expression of myosin light chain (MLC) kinase (MLCK) and MLC phosphorylation. Hypoxia also induces HIF-1 activation by increasing HIF-1α expression, nuclear accumulation, DNA binding activity and target gene expression of HIF-1 in endothelial cells. Knockdown of HIF-1α attenuates endothelial barrier dysfunction and the increased MLCK protein expression induced by hypoxia. Inhibiting the transcription activity of HIF-1 by overexpressing factor inhibiting HIF-1(FIH) prevents the increased MLC phosphorylation and also attenuates endothelial barrier dysfunction in hypoxia. The results suggest that HIF-1α is involved in the MLCK-dependent endothelial barrier dysfunction induced by hypoxia.

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Prolonged hypoxia alters endothelial barrier function

Cited by 7 publications

References 0 publications

Graft vascular function after transplantation of pancreatic islets

Graft vascular function after transplantation of pancreatic islets

Hypoxia-Induced Tumour Cell Migration in an in vivo Chicken Model

Involvement of HIF-1α in MLCK-dependent Endothelial Barrier Dysfunction in Hypoxia

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