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Am J Physiol Heart Circ Physiol 293: H1131-H1137, 2007. First published May 11, 2007; doi:10.1152/ajpheart.01156.2006
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Microvascular network remodeling in dura mater of ovariectomized pigs: role for angiopoietin-1 in estrogen-dependent control of vascular stability

Olga V. Glinskii,1,4,5 Tsghe W. Abraha,2 James R. Turk,3,4 Leona J. Rubin,3,4 Virginia H. Huxley,1,4,* and Vladislav V. Glinsky2,4,5,*

Departments of 1Medical Pharmacology and Physiology, 2Biochemistry, 3Veterinary Biomedical Sciences, and 4National Center for Gender Physiology and Environmental Adaptation, University of Missouri; and 5Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri

Submitted 19 October 2006 ; accepted in final form 6 May 2007

Estrogen 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 threefold decrease in microvessel density and capillary rarefaction and an almost fourfold 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 with 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.

hormones; microcirculation; imaging


Address for reprint requests and other correspondence: V. V. Glinsky, M743 Medical Science Bldg., Dept. of Biochemistry, Univ. of Missouri, Columbia, MO 65212 (e-mail: glinskiivl{at}missouri.edu), and V. H. Huxley, MA 415 Medical Science Bldg., Dept. of Medical Pharmacology and Physiology, Univ. of Missouri, Columbia, MO 65212 (e-mail: huxleyv{at}health.missouri.edu)






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