SEARCH:   Advanced

Blood, 15 January 2006, Vol. 107, No. 2, pp. 550-557. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-05-2047. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-05-2047v1 107/2/550    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Malik, A. K. Articles by Gerber, H.-P. Search for Related Content PubMed PubMed Citation Articles by Malik, A. K. Articles by Gerber, H.-P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Redundant roles of VEGF-B and PlGF during selective VEGF-A blockade in mice Ajay K. Malik, Megan E. Baldwin, Franklin Peale, Germaine Fuh, Wei-Ching Liang, Henry Lowman, Gloria Meng, Napoleone Ferrara, and Hans-Peter Gerber From the Departments of Pathology, Protein Engineering, Antibody Engineering, Assay and Automation Technology, and Molecular Oncology, Genentech, South San Francisco, CA. Vascular endothelial growth factor-A (VEGF-A) and its 2 transmembrane tyrosine-kinase receptors, VEGFR-1 and VEGFR-2, constitute a ligand-receptor signaling system that is crucial for developmental angiogenesis. VEGF-B and placental growth factor (PlGF) activate VEGFR-1 selectively, however, mice lacking either ligand display only minor developmental defects. We hypothesized that the relative contributions of VEGF-B and PlGF to VEGFR-1 signaling may be masked in the presence of VEGF-A, which is abundantly expressed during postnatal development. To test this hypothesis, neonatal or adult mice were treated with a monoclonal antibody (G6-23-IgG) blocking murine VEGF-A or a soluble VEGFR-1 receptor IgG chimeric construct [mFlt(1-3)-IgG], which neutralizes VEGF-A, VEGF-B, and PlGF. Both compounds attenuated growth and survival of neonatal mice to similar extents and the pathophysiologic alterations, including a reduction in organ size and vascularization, changes in gene expression, and hematologic end points, were essentially indistinguishable. In adult mice, we observed only minor changes in response to treatment, which were similar between both anti-VEGF compounds. In conclusion, our findings suggest that PlGF and VEGF-B do not compensate during conditions of VEGF-A blockade, suggesting a minor role for compensatory VEGFR-1 signaling during postnatal development and vascular homeostasis in adults. The absence of compensatory VEGFR-1 signaling by VEGF-B and PlGF may have important implications for the development of anticancer strategies targeting the VEGF ligand/receptor system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. May, D. Gilon, V. Djonov, A. Itin, A. Lazarus, O. Gordon, C. Rosenberger, and E. Keshet Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation PNAS, January 8, 2008; 105(1): 282 - 287. [Abstract] [Full Text] [PDF] S. Yla-Herttuala, T. T. Rissanen, I. Vajanto, and J. Hartikainen Vascular Endothelial Growth Factors: Biology and Current Status of Clinical Applications in Cardiovascular Medicine J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1015 - 1026. [Abstract] [Full Text] [PDF] T. Matsui, M. Kanai-Azuma, K. Hara, S. Matoba, R. Hiramatsu, H. Kawakami, M. Kurohmaru, P. Koopman, and Y. Kanai Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice J. Cell Sci., September 1, 2006; 119(17): 3513 - 3526. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020