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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
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Targeting Cx40 (Connexin40) Expression or Function Reduces Angiogenesis in the Developing Mouse Retina.

Jacques-Antoine Haefliger1, Florent Allagnat2, Lauriane Hamard2

  • 1From the Department of Medicine (J.-A.H., F.A., L.H., L.L.G., F.A.) and Department of Urology (D.N.H.), Lausanne University Hospital, Switzerland; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Switzerland (P.M.); and Centre de Recherche Cardio-Thoracique de Bordeaux (INSERM U1045), Université de Bordeaux, France (E.G., F.A.). florian.alonso@u-bordeaux.fr Jacques-Antoine.Haefliger@chuv.ch.

Arteriosclerosis, Thrombosis, and Vascular Biology
|October 7, 2017
PubMed
Summary

Connexin40 (Cx40) protein is crucial for physiological angiogenesis, regulating vascular growth and maturation in the retina. Loss of Cx40 impairs blood vessel development, highlighting its therapeutic potential for ocular angiogenesis.

Keywords:
Connexin40angiogenesisendotheliumgap junctionsmicephenotype

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Area of Science:

  • Vascular biology
  • Cellular signaling
  • Ophthalmology

Background:

  • Connexin40 (Cx40) facilitates intercellular communication, influencing cardiac electrical conduction and vascular tone.
  • Cx40's role in tumoral angiogenesis is established, but its contribution to physiological angiogenesis remains unclear.

Purpose of the Study:

  • To investigate the role of Cx40 in physiological angiogenesis.
  • To determine if Cx40 regulates vascular growth and development in the retina.

Main Methods:

  • Utilized a mouse neonatal retinal neovascularization model.
  • Genetic deletion and reexpression of Cx40 in endothelial cells.
  • In vitro studies involving microvascular endothelial cell proliferation and PDGF release.
  • In vivo administration of a Cx40 inhibitory peptide.

Main Results:

  • Genetic deletion of Cx40 reduced vascular growth and capillary density in the retina.
  • Cx40 deficiency impaired vessel sprouting and altered mural cell phenotype.
  • Cx40 reexpression restored normal angiogenesis, indicating endothelial cell-specific function.
  • In vitro, Cx40 loss decreased endothelial cell proliferation and increased mural cell chemoattraction.
  • Cx40 inhibition mimicked genetic deletion effects in vivo.

Conclusions:

  • Endothelial Cx40 is essential for physiological angiogenesis in the developing retina.
  • Cx40 regulates early-stage angiogenesis, impacting vessel growth and maturation.
  • Cx40 emerges as a potential therapeutic target for pathological ocular angiogenesis.