Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1

Toffoli, Sébastien; Roegiers, Audrey; Feron, Olivier; Steenbrugge, Martine Van; Ninane, Noëlle; Raes, Martine; Michiels, Carine

doi:10.1007/s10456-009-9131-y

Cited by 83 publications

(73 citation statements)

References 51 publications

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“…As previously mentioned, an increase in endothelial cell migration was evidenced under intermittent hypoxia but not under continuous hypoxia [6]. In this work, we evidenced, by fluorescent 2D-DIGE and western blot analyses, an increase in the abundance of NDRG1 and CRK-I/II under intermittent hypoxia as well as an increase in NDRG1 abundance under continuous hypoxia.…”

Section: Effect Of Ndrg1 or Crk-i/ii Silencing On Endothelial Cell MIsupporting

confidence: 65%

“…Modifications in the behaviour of endothelial cells inside solid tumours have been observed under intermittent and continuous hypoxia. Moreover, numerous data evidence different responses of endothelial cells to these two types of hypoxia [6,10]. However, the molecular mechanisms responsible for these specific responses remain still largely unknown.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous work [6], we evidenced a pro-angiogenic effect of intermittent hypoxia. Indeed, in parallel to the increase in endothelial cell migration, intermittent hypoxia increased the expression of a series of pro-angiogenic genes.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, these proteins are described to play a role in cell migration as well as in angiogenesis. Interestingly, in one of our previous works [6], an increase in endothelial cell migration was evidenced under intermittent hypoxia, suggesting an increase in the angiogenic process in this condition. Therefore, we wanted to study the role played by these two proteins in endothelial cell migration under intermittent as well as continuous hypoxia.…”

Section: D-dige Analysesmentioning

confidence: 91%

“…Moreover, it stimulates proangiogenic behaviour in vitro, that is at least in part due to HIF-1 activation and subsequent VEGF [4] and/or bFGF production [6]. In addition to HIF-1, which is the major regulator of the cell responses to hypoxia, intermittent hypoxia could also activate other transcription factors due to the repetition of cycles of hypoxia and reoxygenation.…”

Section: Introductionmentioning

confidence: 99%

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NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia

et al. 2009

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Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been described to positively influence the tumour growth by modulating the behaviour of cancer cells as well as of endothelial cells. However, the molecular mechanisms regulated by IH still remain poorly understood. In this work, the effects of IH were investigated on endothelial cells by a proteomic approach. Protein abundance variations were studied using fluorescent 2D-Differential in Gel Electrophoresis (2D-DIGE). Amongst the proteins of which the abundance varied under IH, NDRG1 and CRK-I/II were identified by mass spectrometry. These proteins have already been described to influence cancer cell migration as well as the angiogenic processes in solid tumours. Since an increase in endothelial cell migration under IH was evidenced in our previous work, the involvement of NDRG1 and CRK-I/II proteins in endothelial cell migration under IH was determined by silencing the expression of both proteins using siRNA. The results revealed that NDRG1 and CRK-I/II are indeed regulators of endothelial cell migration under intermittent hypoxia: silencing of CRK-I/II resulted in an increase in endothelial cell migration, whereas the invalidation of NDRG1 decreased it. These results give news insight regarding the effects of IH on endothelial cell migration and hence on neoangiogenesis.

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Section: Effect Of Ndrg1 or Crk-i/ii Silencing On Endothelial Cell MIsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: D-dige Analysesmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia

et al. 2009

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Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF‐κB/VEGF pathway

Liu

Yue

et al. 2022

FEBS Open Bio

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Obstructive sleep apnea (OSA) is characterized by the collapse of the soft palate in the upper airway, resulting in chronic intermittent hypoxia during sleep. Therefore, an understanding of the molecular mechanisms underlying pathophysiological dysfunction of the soft palate in OSA is necessary for the development of new therapeutic strategies. In the present study, we observed that high mobility group protein box 1 (HMGB1) was released by a large infiltration of macrophages in the soft palate of OSA patients. The toll‐like receptor 4/nuclear factor kappa B pathway was observed to be activated by the release of HMGB1, and this was accompanied by an increased expression of pro‐inflammatory factors, including tumor necrosis factor‐α and interleukin‐6. Importantly, increased expression of toll‐like receptor 4 was observed in endothelial cells, contributing to upregulation of the angiogenesis‐related factors vascular endothelial‐derived growth factor and matrix metalloproteinase 9. Moreover, we confirmed the effect of the HMGB1‐mediated toll‐like receptor 4/nuclear factor kappa B pathway on cell proliferation and angiogenesis in an in vitro cell model of human umbilical vein endothelial cells. We conclude that HMGB1 may be a potential therapeutic target for preventing angiogenesis and pathology in OSA.

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Design and validation of a pulsatile perfusion bioreactor for 3D high cell density cultures

Chouinard

Gagnon

Couture

et al. 2009

Biotech & Bioengineering

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This study presents the design and validation of a pulsatile flow perfusion bioreactor able to provide a suitable environment for 3D high cell density cultures for tissue engineering applications. Our bioreactor system is mobile, does not require the use of traditional cell culture incubators and is easy to sterilize. It provides real-time monitoring and stable control of pH, dissolved oxygen concentration, temperature, pressure, pulsation frequency, and flow rate. In this bioreactor system, cells are cultured in a gel within a chamber perfused by a culture medium fed by hollow fibers. Human umbilical vein endothelial cells (HUVEC) suspended in fibrin were found to be living, making connections and proliferating up to five to six times their initial seeding number after a 48-h culture period. Cells were uniformly dispersed within the 14.40 mm x 17.46 mm x 6.35 mm chamber. A larger fraction of the cells suspended in 6.35-mm thick gels and cultured in a traditional CO(2) incubator were found to be round and dead [corrected]. In control experiments carried out in a traditional cell culture incubator, the scarcely found living cells were mostly on top of the gels, while cells cultured under perfusion bioreactor conditions were found to be alive and uniformly distributed across the gel.

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Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1

Cited by 83 publications

References 51 publications

NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia

NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia

Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF‐κB/VEGF pathway

Design and validation of a pulsatile perfusion bioreactor for 3D high cell density cultures

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