期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 28, 期 9, 页码 1543-1551出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2008.39
关键词
adeno-associated viral vector; angiogenesis; brain; neovascularization; netrin-1; vascular endothelial growth factor
资金
- NIH [R01 NS27713, R21 NS50668, P01 NS044145]
Netrin-1 is a critical molecule for axonal pathfinding during embryo development, and because of its structural homology to the endothelial mitogens, it may share its effects on vascular network formation. Using an adeno-associated viral netrin-1 vector (AAV-NT-1) gene transfer, we demonstrated that netrin-1 was able to stimulate the proliferation and migration of human cerebral endothelial cells (HCECs) and human aortic smooth muscle cells (HASMCs) compared with the control (P < 0.05), and could also promote HCEC tube formation on matrigel (P < 0.05) in vitro. Moreover, netrin-1 hyperstimulation could promote focal neovascularization (P < 0.05) in the adult brain in vivo. Unlike VEGF-induced microvessel increase, netrin-1-induced newly formed vessels showed an artery-like phenotype, with an intact endothelial cell monolayer surrounded by multiple cell layers, including smooth muscle cells and an astrocyte-connected outer layer. Our findings suggest that netrin-1 plays an important role in promoting blood vessel formation in the adult rodent central nervous system, and could have broad implication in cerebrovascular development and remodeling.
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