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Am J Physiol Heart Circ Physiol (May 11, 2007). doi:10.1152/ajpheart.01156.2006
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Submitted on October 19, 2006
Accepted on May 6, 2007

Microvascular Network Remodeling in Dura Mater of Ovariectomized Pigs: Role for Angiopietin-1 in Estrogen-Dependent Control of Vascular Stability

Olga Glinskii1, Tsghe W Abraha2, James R Turk3, Leona J. Rubin4, Virginia H. Huxley5, and Vladislav V Glinsky2*

1 Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri, United States
2 Biochemistry, University of Missouri-Columbia, Columbia, Missouri, United States
3 Biomedical Sciences, University of Missouri, Columbia, United States
4 Department of Veterinary Biomedical Science, University of Missouri, Columbia, Missouri, United States
5 Dept Medical Pharmacology & Physiology, University of Missouri School of Medicine, Columbia, Missouri, United States; Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri, United States

* To whom correspondence should be addressed. E-mail: glinskiivl{at}missouri.edu.

Estrogen (E2) is a key regulator of vascular responses and angioadaptation in multiple organs and tissues including brain. However, the consequences of a loss of ovarian steroid hormone secretion on the status of microvascular networks in brain and meninges are largely unknown. Here, using the perfused dura mater model coupled with high-resolution digital epifluorescence and laser scanning confocal microscopy and computer-assisted morphometric analysis, we demonstrate that cessation of ovarian hormone production causes dramatic vascular remodeling in meningeal microvascular networks characterized by a 3-fold decrease in microvessel density, capillary rarefaction, and almost 4-fold increase in vascular permeability. These changes were accompanied by a significant decrease in Angiopoietin-1 (Ang-1) expression and Ang-1/Tie-2 ratio (1.4-fold, p<0.01; and 1.5-fold, p<0.05 respectively) in ovariectomized animals compared to intact females, but no changes were detected in the expression of estrogen receptors (ER) {alpha} and {beta}. We conclude that estrogen-dependent control of Ang-1 expression plays an important role in stabilizing meningeal microvessel and maintaining healthy microvascular networks.







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