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Post ovariectomy microvascular destabilization: dura mater network remodeling
Author(s) -
Glinskii Olga,
Glinsky Vladislav,
Abraha Tsghe,
Turk James,
Huxley Virginia
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1215
Subject(s) - dura mater , angiogenesis , microvessel , pericyte , medicine , meninges , stromal cell , endocrinology , estrogen , microcirculation , pathology , chemistry , anatomy , endothelial stem cell , biochemistry , in vitro
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 PLCγ 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.