Abstract
Angiogenesis is a key process in various physiological and pathological conditions in the nervous system and in the retina during postnatal life. Although an increasing number of studies have addressed the role of endothelial cells in this event, the astrocytes contribution in angiogenesis has received less attention. This review is focused on the role of astrocytes as a scaffold and in the stabilization of the new blood vessels, through different molecules release, which can modulate the angiogenesis process in the brain and in the retina. Further, differences in the astrocytes phenotype are addressed in glioblastoma, one of the most devastating types of brain cancer, in order to provide potential targets involved in the cross signaling between endothelial cells, astrocytes and glioma cells, that mediate tumor progression and pathological angiogenesis. Given the relevance of astrocytes in angiogenesis in physiological and pathological conditions, future studies are required to better understand the interrelation between endothelial and astrocyte signaling pathways during this process.
Highlights
Blood vessel growth during early postnatal brain development requires an increase in progenitor cells and their differentiation into astrocytes in the central nervous system [1]
In accordance with this result, an increase in VEGF and Ang-2 expression in astrocytes dependent on the morphogen Sonic Hedgehog (Shh)/nuclear receptor subfamily 2 group F member 2 (NR2F2) pathway was observed in response to oxygen-glucose deprivation, a condition that mimics ischemic insult [85], but in the same model, Shh secreted by activated astrocytes induced proliferation, migration, and tubular formation from endothelial cells (ECs), possibly through the activation of RhoA/Rho associated protein kinase (RhoA/ROCK) pathway in ECs, and not due to other proangiogenic molecules secretion [86]
In vitro studies using cocultures of cerebral microvascular ECs and astrocytes have shown that EETs released by astrocytes stimulates the proliferation and tube formation of ECs, and this was significantly diminished by cytochrome P450 epoxygenases (CYP) inhibitor [94,95], suggesting that EETs acts in a paracrine manner stimulating cerebral angiogenesis
Summary
Blood vessel growth during early postnatal brain development requires an increase in progenitor cells and their differentiation into astrocytes in the central nervous system [1]. Several studies have been focused on determining the role of astrocytes in the angiogenic process from a mechanistic point of view Many of these studies have used the murine retina, an excellent model to study the signaling related to angiogenesis in the central nervous system, the signals released from astrocytes during this process, due its easy anatomical accessibility. Angiogenesis seems to depend on the communication between different cells, such as neurons, glia, ECs, pericytes, and even immune cells in the brain and in the retinal angiogenesis [5–8] These studies show the relevance of the astrocytes in the angiogenesis process during the brain and in retina development angiogenesis, which seems to have similarities regarding the complex mechanisms involved, and where the astrocytes play a key role. We describe the information available about the role of astrocytes in the angiogenic process, during postnatal brain and retinal development, with emphasis on their role as angiogenic guides, the release of pro- or antiangiogenic molecules from astrocytes and the feedback mechanism between astrocytes and blood vessels
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