Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia

We showed previously that angiogenic capillaries in the developing central nervous system express high levels of fibronectin and its receptor α5β1 integrin, and that this expression is developmentally downregulated

Richard Milner; Stephanie Hung; Bernadette Erokwu; Paula Dore-Duffy; Joseph C. LaManna; Gregory J. del Zoppo

2008

Scholarcy highlights

  • The growth of new capillaries occurs in the central nervous system, not just during development, and in a number of conditions within the adult CNS, including brain tumors, arterio-venous malformations, and cerebral ischemia
  • In the current study we used a mouse model of hypobaric hypoxia to examine the influence of cerebral hypoxia on fibronectin and α5β1 integrin expression on angiogenic blood vessels in the CNS
  • We previously demonstrated that during CNS development, angiogenic capillaries show high expression of the α5β1 integrin and its extracellular matrix ligand fibronectin, and that this expression is switched off with blood vessel maturation
  • In light of this finding and the work of others defining an important angiogenic role for the α5β1 integrin in systems outside the CNS, we wanted to examine whether the developmental expression profile of the α5β1 integrin is recapitulated during angiogenesis in the adult CNS
  • In the current study we examined this question in a mouse model of cerebral hypoxia, in which mice are exposed to hypobaric hypoxia for up to 2 weeks, during which time vascular remodeling and increased capillary growth occur
  • Our fundamental observation is that cerebral hypoxia induced a marked transient increase in expression of fibronectin and the α5β1 integrin by cerebral capillaries
  • We are addressing this question by asking which of the well-described angiogenic growth factors or cytokines promote increased expression of the α5β1 integrin on brain capillary endothelial cells in vitro

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