help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Christou, H.
Right arrow Articles by Kourembanas, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Christou, H.
Right arrow Articles by Kourembanas, S.

Am. J. Respir. Cell Mol. Biol., Volume 18, Number 6, June, 1998 768-776

Increased Vascular Endothelial Growth Factor Production in the Lungs of Rats with Hypoxia-induced Pulmonary Hypertension

Helen Christou, Atsushi Yoshida, Victoria Arthur, Toshisuke Morita, and Stella Kourembanas

Joint Program in Neonatology and Division of Surgical Research, Harvard Medical School, Boston, Massachusetts

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.




This article has been cited by other articles:


Home page
 Exp PhysiolHome page
L. Ray, M. Mathieu, P. Jespers, I. Hadad, M. Mahmoudabady, A. Pensis, S. Motte, I. R. Peters, R. Naeije, and K. McEntee
Early increase in pulmonary vascular reactivity with overexpression of endothelin-1 and vascular endothelial growth factor in canine experimental heart failure
Exp Physiol, March 1, 2008; 93(3): 434 - 442.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Fantozzi, O. Platoshyn, A. H. Wong, S. Zhang, C. V. Remillard, M. R. Furtado, O. V. Petrauskene, and J. X.-J. Yuan
Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+ channels in human pulmonary artery smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L993 - L1004.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. K. Eltzschig, M. Faigle, S. Knapp, J. Karhausen, J. Ibla, P. Rosenberger, K. C. Odegard, P. C. Laussen, L. F. Thompson, and S. P. Colgan
Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26
Blood, September 1, 2006; 108(5): 1602 - 1610.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
X. Wu, M. S. Chang, S. A. Mitsialis, and S. Kourembanas
Hypoxia Regulates Bone Morphogenetic Protein Signaling Through C-Terminal-Binding Protein 1
Circ. Res., August 4, 2006; 99(3): 240 - 247.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. F. Voelkel, R. W. Vandivier, and R. M. Tuder
Vascular endothelial growth factor in the lung
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L209 - L221.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
D. Mehta and A. B. Malik
Signaling Mechanisms Regulating Endothelial Permeability
Physiol Rev, January 1, 2006; 86(1): 279 - 367.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. C. Carpenter, S. Schomberg, and K. R. Stenmark
Endothelin-mediated increases in lung VEGF content promote vascular leak in young rats exposed to viral infection and hypoxia
Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L1075 - L1082.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
P. M. Becker, J. Waltenberger, R. Yachechko, T. Mirzapoiazova, J. S.K. Sham, C. G. Lee, J. A. Elias, and A. D. Verin
Neuropilin-1 Regulates Vascular Endothelial Growth Factor-Mediated Endothelial Permeability
Circ. Res., June 24, 2005; 96(12): 1257 - 1265.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A R Kranenburg, W I de Boer, V K T Alagappan, P J Sterk, and H S Sharma
Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease
Thorax, February 1, 2005; 60(2): 106 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. R. Albig and W. P. Schiemann
Identification and Characterization of Regulator of G Protein Signaling 4 (RGS4) as a Novel Inhibitor of Tubulogenesis: RGS4 Inhibits Mitogen-activated Protein Kinases and Vascular Endothelial Growth Factor Signaling
Mol. Biol. Cell, February 1, 2005; 16(2): 609 - 625.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
C.N. Mowa, S. Jesmin, I. Sakuma, S. Usip, H. Togashi, M. Yoshioka, Y. Hattori, and R. Papka
Characterization of Vascular Endothelial Growth Factor (VEGF) in the Uterine Cervix over Pregnancy: Effects of Denervation and Implications for Cervical Ripening
J. Histochem. Cytochem., December 1, 2004; 52(12): 1665 - 1674.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. Budhiraja, R. M. Tuder, and P. M. Hassoun
Endothelial Dysfunction in Pulmonary Hypertension
Circulation, January 20, 2004; 109(2): 159 - 165.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Greenway, R. J. van Suylen, G. Du Marchie Sarvaas, E. Kwan, N. Ambartsumian, E. Lukanidin, and M. Rabinovitch
S100A4/Mts1 Produces Murine Pulmonary Artery Changes Resembling Plexogenic Arteriopathy and Is Increased in Human Plexogenic Arteriopathy
Am. J. Pathol., January 1, 2004; 164(1): 253 - 262.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Fantozzi, S. Zhang, O. Platoshyn, C. V. Remillard, R. T. Cowling, and J. X.-J. Yuan
Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1233 - L1245.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M.-A. Pascaud, F. Griscelli, W. Raoul, E. Marcos, P. Opolon, B. Raffestin, M. Perricaudet, S. Adnot, and S. Eddahibi
Lung Overexpression of Angiostatin Aggravates Pulmonary Hypertension in Chronically Hypoxic Mice
Am. J. Respir. Cell Mol. Biol., October 1, 2003; 29(4): 449 - 457.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
T. Carpenter, S. Schomberg, W. Steudel, J. Ozimek, K. Colvin, K. Stenmark, and D. D. Ivy
Endothelin B Receptor Deficiency Predisposes to Pulmonary Edema Formation via Increased Lung Vascular Endothelial Cell Growth Factor Expression
Circ. Res., September 5, 2003; 93(5): 456 - 463.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. Louzier, B. Raffestin, A. Leroux, D. Branellec, J. M. Caillaud, M. Levame, S. Eddahibi, and S. Adnot
Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L926 - L937.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Hanaoka, Y. Droma, A. Naramoto, T. Honda, T. Kobayashi, and K. Kubo
Vascular endothelial growth factor in patients with high-altitude pulmonary edema
J Appl Physiol, May 1, 2003; 94(5): 1836 - 1840.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. R. Grover, T. A. Parker, J. P. Zenge, N. E. Markham, J. P. Kinsella, and S. H. Abman
Intrauterine hypertension decreases lung VEGF expression and VEGF inhibition causes pulmonary hypertension in the ovine fetus
Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L508 - L517.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
K. L. Jones, H. F. Krous, J. Nadeau, B. Blackbourne, H. R. Zielke, and D. Gozal
Vascular Endothelial Growth Factor in the Cerebrospinal Fluid of Infants Who Died of Sudden Infant Death Syndrome: Evidence for Antecedent Hypoxia
Pediatrics, February 1, 2003; 111(2): 358 - 363.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Fujita, R. J. Mason, C. Cool, J. M. Shannon, N. Hara, and K. A. Fagan
Pulmonary hypertension in TNF-alpha -overexpressing mice is associated with decreased VEGF gene expression
J Appl Physiol, December 1, 2002; 93(6): 2162 - 2170.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Pham, T. Uchida, C. Planes, L. B. Ware, R. Kaner, M. A. Matthay, and C. Clerici
Hypoxia upregulates VEGF expression in alveolar epithelial cells in vitro and in vivo
Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1133 - L1142.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. C Wanstall, A. Gambino, T. K Jeffery, M. M Cahill, D. Bellomo, N. K Hayward, and G. F Kay
Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension
Cardiovasc Res, August 1, 2002; 55(2): 361 - 368.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. D. Chan, D. V. Morales, C. H. Welsh, M. T. McDermott, and M. I. Schwarz
Calcium Deposition with or without Bone Formation in the Lung
Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1654 - 1669.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. P. Taylor, L. Osorio, R. Craig, J. A. Raleigh, Z. Ying, D. M. Goldenberg, and R. D. Blumenthal
Tumor-specific Regulation of Angiogenic Growth Factors and Their Receptors during Recovery from Cytotoxic Therapy
Clin. Cancer Res., April 1, 2002; 8(4): 1213 - 1222.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Minamino, H. Christou, C.-M. Hsieh, Y. Liu, V. Dhawan, N. G. Abraham, M. A. Perrella, S. A. Mitsialis, and S. Kourembanas
Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia
PNAS, July 5, 2001; (2001) 161272598.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. A. Fagan
Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia
J Appl Physiol, June 1, 2001; 90(6): 2502 - 2507.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
M. Levi, L. Moons, A. Bouche, S. D. Shapiro, D. Collen, and P. Carmeliet
Deficiency of Urokinase-Type Plasminogen Activator-Mediated Plasmin Generation Impairs Vascular Remodeling During Hypoxia-Induced Pulmonary Hypertension in Mice
Circulation, April 17, 2001; 103(15): 2014 - 2020.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
I. M. Olfert, E. C. Breen, O. Mathieu-Costello, and P. D. Wagner
Chronic hypoxia attenuates resting and exercise-induced VEGF, flt-1, and flk-1 mRNA levels in skeletal muscle
J Appl Physiol, April 1, 2001; 90(4): 1532 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. Partovian, S. Adnot, B. Raffestin, V. Louzier, M. Levame, I. M. Mavier, P. Lemarchand, and S. Eddahibi
Adenovirus-Mediated Lung Vascular Endothelial Growth Factor Overexpression Protects against Hypoxic Pulmonary Hypertension in Rats
Am. J. Respir. Cell Mol. Biol., December 1, 2000; 23(6): 762 - 771.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. A. Kazi, W. S. Lee, E. Wagner, and P. M. Becker
VEGF, fetal liver kinase-1, and permeability increase during unilateral lung ischemia
Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L460 - L467.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. Maloney, D. Wang, T. Duncan, N. Voelkel, and S. Ruoss
Plasma Vascular Endothelial Growth Factor in Acute Mountain Sickness
Chest, July 1, 2000; 118(1): 47 - 52.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
H. Christou, T. Morita, C.-M. Hsieh, H. Koike, B. Arkonac, M. A. Perrella, and S. Kourembanas
Prevention of Hypoxia-Induced Pulmonary Hypertension by Enhancement of Endogenous Heme Oxygenase-1 in the Rat
Circ. Res., June 23, 2000; 86(12): 1224 - 1229.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
P. M. Becker, A. Alcasabas, A. Y. Yu, G. L. Semenza, and T. E. Bunton
Oxygen-Independent Upregulation of Vascular Endothelial Growth Factor and Vascular Barrier Dysfunction during Ventilated Pulmonary Ischemia in Isolated Ferret Lungs
Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 272 - 279.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Minamino, H. Christou, C.-M. Hsieh, Y. Liu, V. Dhawan, N. G. Abraham, M. A. Perrella, S. A. Mitsialis, and S. Kourembanas
Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia
PNAS, July 17, 2001; 98(15): 8798 - 8803.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1998 American Thoracic Society.