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    Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension

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    Authors
    Christou, Helen
    Yoshida, Atsushi
    Arthur, Victoria
    Morita, Toshisuke
    Kourembanas, Stella
    Document Type
    Journal Article
    Publication Date
    1998-06-25
    Keywords
    Animals
    Anoxia
    Blotting, Northern
    Capillary Permeability
    Endothelial Growth Factors
    Hypertension, Pulmonary
    Immunohistochemistry
    In Situ Hybridization
    Lung
    Lymphokines
    Male
    Pulmonary Alveoli
    RNA, Messenger
    Rats
    Rats, Sprague-Dawley
    Receptor Protein-Tyrosine Kinases
    Receptors, Growth Factor
    Receptors, Vascular Endothelial Growth Factor
    Time Factors
    Vascular Endothelial Growth Factor A
    Vascular Endothelial Growth Factors
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    http://ajrcmb.atsjournals.org/cgi/content/full/18/6/768
    Abstract
    Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability factor targeting predominantly endothelial cells. At least two tyrosine kinase receptors, Flk-1 and Flt-1, mediate its action and are mostly expressed by endothelial cells. VEGF and VEGF receptor expression are upregulated by hypoxia in vivo and the role of VEGF in hypoxia-induced angiogenesis has been extensively studied in a variety of disease entities. Although VEGF and its receptors are abundantly expressed in the lung, their role in hypoxic pulmonary hypertension and the accompanying vascular remodeling are incompletely understood. We report in this in vivo study that hypoxia increases mRNA levels for both VEGF and Flk-1 in the rat lung. The kinetics of the hypoxic response differ between receptor and ligand: Flk-1 mRNA showed a biphasic response to hypoxia with a significant, but transient, rise in mRNA levels observed after 9-15 h of hypoxic exposure and the highest levels noted after 3 wk. In contrast, VEGF mRNA levels did not show a significant increase with acute hypoxia, but increased progressively after 1-3 wk of hypoxia. By in situ hybridization, VEGF mRNA was localized predominantly in alveolar epithelial cells with increased signal in the lungs of hypoxic animals compared with controls. Immunohistochemical staining with anti-VEGF antibodies localized VEGF peptide throughout the lung parenchyma and was increased in hypoxic compared with normoxic animals. Furthermore, hypoxic animals had significantly higher circulating VEGF concentrations compared with normoxic controls. Lung vascular permeability as measured by extravasation of Evans Blue dye was not significantly different between normoxic and hypoxic animals, although a tendency for increased permeability was seen in the hypoxic animals. These findings suggest a possible role for VEGF in the pulmonary response to hypoxia.
    Source
    Am J Respir Cell Mol Biol. 1998 Jun;18(6):768-76.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49417
    PubMed ID
    9618381
    Notes
    Medical student Victoria Arthur participated in this study as part of the Senior Scholars research program.
    Related Resources
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    T.H. Chan School of Medicine Student Publications
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      Covassin, Laurence D.; Villefranc, Jacques A.; Kacergis, Michael C.; Weinstein, Brant M.; Lawson, Nathan D. (2006-04-18)
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      Hypoxic responses of vascular cells

      Kourembanas, Stella; Morita, Toshisuke; Christou, Helen; Liu, Yuxiang; Koike, Hideo; Brodsky, Dara; Arthur, Victoria; Mitsial, S. Alex (1998-07-24)
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      Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells

      Chung, Jun; Bachelder, Robin E.; Lipscomb, Elizabeth A.; Shaw, Leslie M.; Mercurio, Arthur M. (2002-07-10)
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