title: Microvascular network remodeling in dura mater of ovariectomized pigs: role for angiopoietin-1 in estrogen-dependent control of vascular stability.
abstract: 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.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Glinskii
authors.forename: Tsghe W
authors.initials: TW
authors.lastname: Abraha
authors.forename: James R
authors.initials: JR
authors.lastname: Turk
authors.forename: Leona J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Virginia H
authors.initials: VH
authors.lastname: Huxley
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Glinsky
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability; D015536:Down-Regulation; D004388:Dura Mater / Q000098:blood supply*; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D007090:Image Interpretation, Computer-Assisted; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D010052:Ovariectomy; D042787:Receptor, TIE-2 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
chemical_list: D042683:Angiopoietin-1; D004967:Estrogens; D011960:Receptors, Estrogen; D042787:Receptor, TIE-2