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Diminished Ang‐2 Expression and Microvascular Density in COX‐2 Knock‐out Mouse Cerebral Cortex in Moderate Hypobaric Hypoxia
Author(s) -
Benderro Girriso,
Xu Kui,
LaManna Joseph
Publication year - 2015
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.29.1_supplement.706.8
Subject(s) - hypoxia (environmental) , angiogenesis , western blot , immunohistochemistry , endocrinology , medicine , cerebral cortex , biology , chemistry , oxygen , biochemistry , gene , organic chemistry
Normal brain function is dependent on continuous and controlled oxygen delivery. Prolonged hypoxia leads to angiogenesis, suggesting a modulatory role for oxygen in expression of angiogenic factors that are responsible for brain microvascular adaptational plasticity. Angiopoetin‐2 (Ang‐2) is one of the critical molecules in brain microvascular remodeling in order to regulate cerebral oxygen homeostasis. The objective of this study was to determine effects of cyclooxygenase‐2 (COX‐2) knock‐out (KO) on Ang‐2 expression and microvascular remodeling in the mouse cerebral cortexduring prolonged moderate hypobaric hypoxia. Three month old male COX‐2 gene KO and wild type (WT) mice were kept in a 0.4 ATM (290 torr) hypobaric hypoxia chamber for up to 21 days. Normoxic littermates were kept in the same room outside the chamber. The mice were sacrificed and brain samples collected were either lysated for Western blot protein analysis or paraffin embedded for immunohistochemistry (IHC), to determine microvascular count. Compared to wild type mice, we observed attenuated Ang‐2 protein induction in COX‐2 KO mice in hypoxic conditions. Baseline capillary count in normoxia is similar in both WT and COX‐2 KO mice, but hypoxia induced angiogenesis (microvascular density) was recorded to be diminished in COX‐2 KO mice compared to wild type cohorts during prolonged hypoxic conditions. These results imply the importance of COX‐2 in expression of important vascular remodeling protein (Ang‐2), and brain microvascular angioplasticity to acclimatize to ambient oxygen availability. This study was supported by National Institute of Health grant NS 38632.