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AMPK and Akt crosstalk controls dura mater post ovariectomy (OVX) microvascular remodeling in pigs
Author(s) -
Glinskii Olga V,
Glinsky Vladislav,
Abraha Tsghe,
Huxley Virginia
Publication year - 2008
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.22.1_supplement.925.14
Subject(s) - protein kinase b , angiogenesis , ampk , pi3k/akt/mtor pathway , crosstalk , endocrinology , estrogen , medicine , protein kinase a , phosphorylation , chemistry , microbiology and biotechnology , hypoxia (environmental) , signal transduction , cancer research , biology , physics , organic chemistry , oxygen , optics
Microvascular remodeling associated with the onset of reproductive senescence is a complex multi‐step process. Recently, we demonstrated that cessation of ovarian hormone production causes dramatic remodeling of meningeal microvascular networks, characterized by significant capillary rarefaction. However, the initial estrogen‐dependent post OVX loss of microvessels triggers stromal and vascular hypoxic responses leading to an increase in HIF‐1α expression and PDGF/VEGF system activation. Concomitant attenuation of hypoxia‐induced phosphorylation of AMP‐activated protein kinase (AMPK), caused by reduced estrogen (E2) levels, contributes to the activation of Akt and mTOR/p70S6K pathways, thereby promoting enhanced protein synthesis and prompting new vessel growth. Indeed, 2 months post OVX, we observed considerable angiogenic activity in meningeal microvascular networks that underwent previous regression. In summary our results demonstrate that post OVX angioadaptation proceeds through distinct stages regulated tightly on multiple levels by a complex interplay between several major signaling pathways induced by an array of internal and external metabolic stimuli. Supported by: NASA NNJ05HF37G, VA Merit Review Award, and NIH HL078816, HL075186, RR017353.