Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro

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• 作者：Chow ; Jen ; Ogunshola ; Omolara ; Fan ; Shou-Yuan ; Li ; Yan ; Ment ; Laura R. ; Madri ; Joseph A.
• 关键词：Disorders of the nervous system ; Ischemia ; Endothelial cell ; Glia ; Hypoxia ; VEGF ; Apoptosis ; Survival
• 刊名：Developmental Brain Research
• 出版年：2001
• 出版时间：September 23, 2001
• 年：2001
• 卷：130
• 期：1
• 页码：123-132
• 全文大小：1.31 M

文摘

Chronic sublethal hypoxia has been associated with changes in neurovascular behavior, mediated, in part, by induction of vascular endothelial growth factor-A (VEGF-A₁₆₅). In this report we demonstrate that RBE4 cells (derived from rodent cerebral microvasculature), when cultured in three-dimensional collagen gels: (1) Are induced to undergo increased tube formation in response to VEGF-A₁₆₅ in a dose-dependent manner; (2) undergo apoptosis under mild hypoxic conditions; (3) are rescued from the effects of hypoxia by the addition of exogenous VEGF-A₁₆₅ in a dose-dependent and inhibitable manner or by co-culture with primary newborn rat astrocytes, which are induced to express increased amounts of VEGF-A in hypoxic conditions. Further, we demonstrate that: (4) The observed astrocyte-produced, VEGF-mediated protection from apoptosis (survival) is inhibitable with soluble recombinant VEGF receptor-1 (sFlt), and is associated with a robust induction of MAPK tyrosine phosphorylation. These findings illustrate the importance of VEGF in the process of neurovascular survival in response to injury in developing brain and provide insight into the signaling pathways involved.