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(The FASEB Journal. 2007;21:897.13)
© 2007 FASEB
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897.13

Post ovariectomy microvascular destabilization: dura mater network remodeling

Olga Glinskii1,2, Vladislav Glinsky1,3, Tsghe Abraha1, James Turk1 and Virginia Huxley1,2

1 University of Missouri, Columbia, MA415 Med Sci Bldg, Columbia, MO, 65212,
2 National Center for Gender Physiology, MA415 Med Sci Bldg, Columbia, MO, 65212,
3 Harry S Truman Memorial Veterans’ Hospital, 800 Hospital Dr, Columbia, MO, 65201

ABSTRACT

Our recent results demonstrate that cessation of ovarian hormone production causes dramatic meningeal microvascular network remodeling, characterized by significant capillary rarefaction. Even 2 months post-ovariectomy (OVX) pig dura mater microvessels remain destabilized due to reduced angiopoietin-1 expression. From this state either further regression or angiogenesis could occur. We tested the hypothesis that initial estrogen-dependent meningeal microvessel loss following OVX triggers stromal and vascular hypoxic responses aimed at restoring dura microvasculature. We demonstrate that 2 months post-OVX there is activation of the PDGF/VEGF system in the dura mater stroma and microvasculature that is accompanied by a shift in the balance between PI3K and PLC{gamma} activity downstream of PDGF/VEGF signaling toward PI3K. It appears that the latter serves as a molecular switch favoring angiogenic responses rather than further regression of the destabilized microvessels. Consistent with this idea we have found considerable angiogenic activity in meningeal microvascular networks that underwent previous regression. Our results indicate that angioadaptation of meningeal microvessels in response to cessation of ovarian hormone production is not a unidirectional, but a complex multistage process regulated on multiple levels.

Supported by: AHA Heartland Affiliate Postdoctoral Fellowship.





This Article
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Right arrow Articles by Huxley, V.