Increased expression of fibronectin and the alpha 5 beta 1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia.
The extracellular matrix (ECM) is an important regulator of angiogenesis and vascular remodeling. We showed previously that angiogenic capillaries in the developing CNS express high levels of fibronectin and its receptor alpha5beta1 integrin, and that this expression is developmentally downregulated. As cerebral hypoxia leads to an angiogenic response, we sought to determine whether angiogenic vessels in the adult CNS re-express fibronectin and the alpha5beta1 integrin. Ten-week old mice were subject to hypobaric hypoxia for 0, 4, 7 and 14 days, and fibronectin/integrin expression examined. Fibronectin and the alpha5 integrin subunit were strongly upregulated on capillaries in the hypoxic CNS, with the effect maximal at the earliest time point examined (4 days). Immunofluorescent studies demonstrated that the alpha5 integrin was expressed by angiogenic endothelial cells. In light of the defined angiogenic role for fibronectin in other systems, this work suggests that induction of fibronectin-alpha5beta1 integrin expression may be an important molecular switch driving angiogenesis in the hypoxic CNS.
Milner
Richard
R
Department of Molecular and Experimental Medicine, MEM-132, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. rmilner@scripps.edu
Hung
Stephanie
S
Erokwu
Bernadette
B
Dore-Duffy
Paula
P
LaManna
Joseph C
JC
del Zoppo
Gregory J
GJ
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000235:genetics; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D039081:Integrin alpha5beta1 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology
D005353:Fibronectins; D039081:Integrin alpha5beta1