First Author | Li L | Year | 2012 |
Journal | Exp Neurol | Volume | 237 |
Issue | 1 | Pages | 46-54 |
PubMed ID | 22721769 | Mgi Jnum | J:187182 |
Mgi Id | MGI:5435643 | Doi | 10.1016/j.expneurol.2012.06.005 |
Citation | Li L, et al. (2012) An angiogenic role for the alpha5beta1 integrin in promoting endothelial cell proliferation during cerebral hypoxia. Exp Neurol 237(1):46-54 |
abstractText | Fibronectin is a critical regulator of vascular modelling, both in development and in the adult. In the hypoxic adult central nervous system (CNS), fibronectin is induced on angiogenic vessels, and endothelial cells show strong induction of the two fibronectin receptors alpha5beta1 and alphavbeta3 integrins. In a previous study, we found that the alphavbeta3 integrin is dispensable for hypoxic-induced cerebral angiogenesis, but a role for the endothelial alpha5beta1 integrin was suggested. To directly investigate the role of endothelial alpha5 integrin in cerebral angiogenesis, wild-type mice and mice lacking alpha5 integrin expression in endothelial cells (alpha5-EC-KO) were subject to hypoxia (8% O(2)) for 0, 2, 4, 7 or 14 days. Quantification of cerebral vessel density and endothelial-specific proteins claudin-5 and Glut-1 revealed that alpha5-EC-KO mice displayed an attenuated angiogenic response, which correlated with delayed endothelial proliferation. alpha5-EC-KO mice showed no defect in the ability to organize a cerebrovascular fibronectin matrix, and no compensatory increase in vascular alphavbeta3 integrin expression. Consistent with these findings, primary alpha5KO brain endothelial cells (BEC) in culture exhibited delayed growth and proliferation. Taken together, these studies demonstrate an important angiogenic role for the alpha5beta1 integrin in promoting BEC proliferation in response to cerebral hypoxia. |