03/08
2012
Seminar

Is Fibronectin a Major Driver of Cerebral Angiogenesis?

12:00 pm - 12:00 pm
Alfond Room 304
Biddeford Campus
Richard Milner, M.D., Ph.D.

Free and open to the public

The extracellular matrix (ECM) is an important regulator of angiogenesis and vascular remodeling. We have shown that angiogenic vessels in the developing central nervous system (CNS) express high levels of fibronectin and the fibronectin receptor 伪5尾1 integrin. In keeping with an angiogenic role for fibronectin in other systems, this implies that fibronectin may provide an important angiogenic drive in the CNS. To investigate whether this mechanism also applies to the adult CNS, we examined these events in a mouse model of cerebral hypoxia, in which mice are exposed to 8% O2. Over a 2-week period, this results in a robust increase (50%) in vessel density in the brains of these mice. Immunohistochemistry and western blot revealed that hypoxia strongly induced fibronectin and brain endothelial cell (BEC) expression of the fibronectin receptors, 伪5尾1 and 伪v尾3 integrins. To directly test whether these BEC integrins are required for cerebral angiogenesis, the hypoxic response was examined in transgenic mice deficient in either the 伪5 or 尾3 integrins. 尾3 integrin KO mice showed no obvious defect in the angiogenic response, and actually showed an increased BEC mitotic index, which correlated with compensatory increased 伪5 integrin expression. In contrast, mice lacking endothelial expression of 伪5 integrins (伪5-EC-KO mice) showed an attenuated angiogenic response which was paralleled by delayed BEC proliferation. Taken together, these studies suggest that 伪v尾3 integrin is not essential for cerebral angiogenesis, but demonstrate an important angiogenic role for the 伪5尾1 integrin in promoting BEC proliferation. 

Lunch will be provided.

Hosted by: Dr. Colin Willis

Address

Alfond Room 304
United States