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Vascular adaptation in dura and pia mater of ovariectomized pigs employs different molecular mechanisms
Author(s) -
Glinskii Olga,
Glinsky Vladislav,
Abraha Tsghe,
Huxley Virginia
Publication year - 2009
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.23.1_supplement.592.21
Subject(s) - endocrinology , medicine , ovariectomized rat , protein kinase b , downregulation and upregulation , chemistry , pi3k/akt/mtor pathway , receptor , signal transduction , microbiology and biotechnology , estrogen , biology , biochemistry , gene
Cessation of the ovarian hormone production leads to a reduction in plasma estradiol (E2), and aromatization at extragonadal sites (brain, bones, adipose) becomes the primary sources of E2 production after menopause. Previously, we demonstrated that dura mater (DM) microvascular networks of ovariectomized (OVX) pigs undergo dramatic remodeling, characterized by capillary loss and increased vessel permeability. The analysis of growth factors and receptors as well as downstream signaling pathways revealed that in DM, which depends on plasma E2 supply, the initial E2‐dependent microvessels loss triggers hypoxic responses manifested by an increase in HIF‐1α expression and PDGF/VEGF system activation. Concomitant attenuation of hypoxia‐induced AMPK phosphorylation caused by reduced E2 levels contributes to activation of Akt and mTOR/p70S6K pathways promoting enhanced protein synthesis and new vessel growth. In contrast, in pia mater (PM) microvessels that benefit from local E2 production by the brain, there was no change in HIF‐1α expression or Akt activation following OVX, while estrogen receptor β was upregulated suggesting active signaling through this receptor by the locally produced E2. Our results suggest that post OVX angioadaptation in DM and PM may involve different molecular pathways depending on local E2 availability. Supported by AHA National SDG 0830287N, NIH HL078816, HL075186, RR017353.