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Development, Vol 126, Issue 6 1149-1159, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

VEGF is required for growth and survival in neonatal mice

HP Gerber, KJ Hillan, AM Ryan, J Kowalski, GA Keller, L Rangell, BD Wright, F Radtke, M Aguet and N Ferrara
Departments of Cardiovascular Research and Pathology, Genentech, Inc., South San Francisco, CA 94080, USA.

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.
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Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L134 - L142.
[Abstract] [Full Text] [PDF]

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K. Tang, E. C. Breen, H.-P. Gerber, N. M. A. Ferrara, and P. D. Wagner
Capillary regression in vascular endothelial growth factor-deficient skeletal muscle
Physiol Genomics, June 17, 2004; 18(1): 63 - 69.
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R. D. Galiano, O. M. Tepper, C. R. Pelo, K. A. Bhatt, M. Callaghan, N. Bastidas, S. Bunting, H. G. Steinmetz, and G. C. Gurtner
Topical Vascular Endothelial Growth Factor Accelerates Diabetic Wound Healing through Increased Angiogenesis and by Mobilizing and Recruiting Bone Marrow-Derived Cells
Am. J. Pathol., June 1, 2004; 164(6): 1935 - 1947.
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H. Rossiter, C. Barresi, J. Pammer, M. Rendl, J. Haigh, E. F. Wagner, and E. Tschachler
Loss of Vascular Endothelial Growth Factor A Activity in Murine Epidermal Keratinocytes Delays Wound Healing and Inhibits Tumor Formation
Cancer Res., May 15, 2004; 64(10): 3508 - 3516.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
A. K. Nath, J. Enciso, M. Kuniyasu, X.-Y. Hao, J. A. Madri, and E. Pinter
Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy
Development, May 15, 2004; 131(10): 2485 - 2496.
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D. M. Roberts, J. B. Kearney, J. H. Johnson, M. P. Rosenberg, R. Kumar, and V. L. Bautch
The Vascular Endothelial Growth Factor (VEGF) Receptor Flt-1 (VEGFR-1) Modulates Flk-1 (VEGFR-2) Signaling During Blood Vessel Formation
Am. J. Pathol., May 1, 2004; 164(5): 1531 - 1535.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
E. Zelzer, R. Mamluk, N. Ferrara, R. S. Johnson, E. Schipani, and B. R. Olsen
VEGFA is necessary for chondrocyte survival during bone development
Development, May 1, 2004; 131(9): 2161 - 2171.
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F. Baffert, G. Thurston, M. Rochon-Duck, T. Le, R. Brekken, and D. M. McDonald
Age-Related Changes in Vascular Endothelial Growth Factor Dependency and Angiopoietin-1-Induced Plasticity of Adult Blood Vessels
Circ. Res., April 16, 2004; 94(7): 984 - 992.
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C. N. Roybal, S. Yang, C.-W. Sun, D. Hurtado, D. L. Vander Jagt, T. M. Townes, and S. F. Abcouwer
Homocysteine Increases the Expression of Vascular Endothelial Growth Factor by a Mechanism Involving Endoplasmic Reticulum Stress and Transcription Factor ATF4
J. Biol. Chem., April 9, 2004; 279(15): 14844 - 14852.
[Abstract] [Full Text] [PDF]

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R. Walczak, S. B. Joseph, B. A. Laffitte, A. Castrillo, L. Pei, and P. Tontonoz
Transcription of the Vascular Endothelial Growth Factor Gene in Macrophages Is Regulated by Liver X Receptors
J. Biol. Chem., March 12, 2004; 279(11): 9905 - 9911.
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E. Varfolomeev, F. Kischkel, F. Martin, D. Seshasayee, H. Wang, D. Lawrence, C. Olsson, L. Tom, S. Erickson, D. French, et al.
APRIL-Deficient Mice Have Normal Immune System Development
Mol. Cell. Biol., February 1, 2004; 24(3): 997 - 1006.
[Abstract] [Full Text] [PDF]

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V. Tsatsaris, F. Goffin, C. Munaut, J.-F. Brichant, M.-R. Pignon, A. Noel, J.-P. Schaaps, D. Cabrol, F. Frankenne, and J.-M. Foidart
Overexpression of the Soluble Vascular Endothelial Growth Factor Receptor in Preeclamptic Patients: Pathophysiological Consequences
J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5555 - 5563.
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P. B. Freeburg and D. R. Abrahamson
Hypoxia-Inducible Factors and Kidney Vascular Development
J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2723 - 2730.
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T. D. Le Cras, W. D. Hardie, K. Fagan, J. A. Whitsett, and T. R. Korfhagen
Disrupted pulmonary vascular development and pulmonary hypertension in transgenic mice overexpressing transforming growth factor-{alpha}
Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1046 - L1054.
[Abstract] [Full Text] [PDF]

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H Yoshiji, S Kuriyama, J Yoshii, Y Ikenaka, R Noguchi, D J Hicklin, Y Wu, K Yanase, T Namisaki, M Yamazaki, et al.
Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis
Gut, September 1, 2003; 52(9): 1347 - 1354.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
A. Nalbandian, L. Dettin, M. Dym, and N. Ravindranath
Expression of Vascular Endothelial Growth Factor Receptors During Male Germ Cell Differentiation in the Mouse
Biol Reprod, September 1, 2003; 69(3): 985 - 994.
[Abstract] [Full Text] [PDF]

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R. M. Tuder, L. Zhen, C. Y. Cho, L. Taraseviciene-Stewart, Y. Kasahara, D. Salvemini, N. F. Voelkel, and S. C. Flores
Oxidative Stress and Apoptosis Interact and Cause Emphysema Due to Vascular Endothelial Growth Factor Receptor Blockade
Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 88 - 97.
[Abstract] [Full Text] [PDF]

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V. Easwaran, S. H. Lee, L. Inge, L. Guo, C. Goldbeck, E. Garrett, M. Wiesmann, P. D. Garcia, J. H. Fuller, V. Chan, et al.
{beta}-Catenin Regulates Vascular Endothelial Growth Factor Expression in Colon Cancer
Cancer Res., June 15, 2003; 63(12): 3145 - 3153.
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H. Sugimoto, Y. Hamano, D. Charytan, D. Cosgrove, M. Kieran, A. Sudhakar, and R. Kalluri
Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria
J. Biol. Chem., April 4, 2003; 278(15): 12605 - 12608.
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P. B. Freeburg, B. Robert, P. L. St. John, and D. R. Abrahamson
Podocyte Expression of Hypoxia-Inducible Factor (HIF)-1 and HIF-2 during Glomerular Development
J. Am. Soc. Nephrol., April 1, 2003; 14(4): 927 - 938.
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 DevelopmentHome page
A. Damert, L. Miquerol, M. Gertsenstein, W. Risau, and A. Nagy
Insufficient VEGFA activity in yolk sac endoderm compromises haematopoietic and endothelial differentiation
Development, March 6, 2003; 129(8): 1881 - 1892.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. LeCouter, R. Lin, M. Tejada, G. Frantz, F. Peale, K. J. Hillan, and N. Ferrara
The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells
PNAS, March 4, 2003; 100(5): 2685 - 2690.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
H. Pavenstadt, W. Kriz, and M. Kretzler
Cell Biology of the Glomerular Podocyte
Physiol Rev, January 1, 2003; 83(1): 253 - 307.
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X. Zhao, X. Lu, and Q. Feng
Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis
Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2371 - H2378.
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C. Ruhrberg, H. Gerhardt, M. Golding, R. Watson, S. Ioannidou, H. Fujisawa, C. Betsholtz, and D. T. Shima
Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis
Genes & Dev., October 15, 2002; 16(20): 2684 - 2698.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
R Mahadeva and S D Shapiro
Chronic obstructive pulmonary disease * 3: Experimental animal models of pulmonary emphysema
Thorax, October 1, 2002; 57(10): 908 - 914.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
P. P. Young, A. A. Hofling, and M. S. Sands
VEGF increases engraftment of bone marrow-derived endothelial progenitor cells (EPCs) into vasculature of newborn murine recipients
PNAS, September 3, 2002; 99(18): 11951 - 11956.
[Abstract] [Full Text] [PDF]

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E. Geva, D. G. Ginzinger, C. J. Zaloudek, D. H. Moore, A. Byrne, and R. B. Jaffe
Human Placental Vascular Development: Vasculogenic and Angiogenic (Branching and Nonbranching) Transformation Is Regulated by Vascular Endothelial Growth Factor-A, Angiopoietin-1, and Angiopoietin-2
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4213 - 4224.
[Abstract] [Full Text] [PDF]

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T. D. Le Cras, N. E. Markham, R. M. Tuder, N. F. Voelkel, and S. H. Abman
Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure
Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L555 - L562.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. Holash, S. Davis, N. Papadopoulos, S. D. Croll, L. Ho, M. Russell, P. Boland, R. Leidich, D. Hylton, E. Burova, et al.
VEGF-Trap: A VEGF blocker with potent antitumor effects
PNAS, August 20, 2002; 99(17): 11393 - 11398.
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C. Galambos, Y.-S. Ng, A. Ali, A. Noguchi, S. Lovejoy, P. A. D'Amore, and D. E. deMello
Defective Pulmonary Development in the Absence of Heparin-Binding Vascular Endothelial Growth Factor Isoforms
Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 194 - 203.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
A. Flyvbjerg, B. F. Schrijvers, A. S. De Vriese, R. G. Tilton, and R. Rasch
Compensatory glomerular growth after unilateral nephrectomy is VEGF dependent
Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E362 - E366.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
L. Jussila and K. Alitalo
Vascular Growth Factors and Lymphangiogenesis
Physiol Rev, July 1, 2002; 82(3): 673 - 700.
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T. Odorisio, C. Schietroma, M. L. Zaccaria, F. Cianfarani, C. Tiveron, L. Tatangelo, C. M. Failla, and G. Zambruno
Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability
J. Cell Sci., June 15, 2002; 115(12): 2559 - 2567.
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A. N. Witmer, J. Dai, H. A. Weich, G. F.J.M. Vrensen, and R. O. Schlingemann
Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia
J. Histochem. Cytochem., June 1, 2002; 50(6): 767 - 778.
[Abstract] [Full Text] [PDF]


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