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Science 16 October 1998:
Vol. 282. no. 5388, pp. 468 - 471
DOI: 10.1126/science.282.5388.468
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Reports

Increased Vascularization in Mice Overexpressing Angiopoietin-1

Chitra Suri, Joyce McClain, Gavin Thurston, Donald M. McDonald, Hao Zhou, Eben H. Oldmixon, Thomas N. Sato, George D. Yancopoulos *

The angiopoietins and members of the vascular endothelial growth factor (VEGF) family are the only growth factors thought to be largely specific for vascular endothelial cells. Targeted gene inactivation studies in mice have shown that VEGF is necessary for the early stages of vascular development and that angiopoietin-1 is required for the later stages of vascular remodeling. Here it is shown that transgenic overexpression of angiopoietin-1 in the skin of mice produces larger, more numerous, and more highly branched vessels. These results raise the possibility that angiopoietins can be used, alone or in combination with VEGF, to promote therapeutic angiogenesis.

C. Suri, J. McClain, H. Zhou, G. D. Yancopoulos, Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. G. Thurston and D. M. McDonald, Department of Anatomy and Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA. E. H. Oldmixon, Rogers Imaging, Needham, MA 02192, USA. T. N. Sato, University of Texas, Southwestern Medical Center, Dallas, TX 75235, USA.
*   To whom correspondence should be addressed. E-mail: gdy{at}regpha.com

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Temporally Compartmentalized Expression of Ephrin-B2 during Renal Glomerular Development.
T. Takahashi, K. Takahashi, S. Gerety, H. Wang, D. J. Anderson, and T. O. Daniel (2001)
J. Am. Soc. Nephrol. 12, 2673-2682
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Increased Renal Angiopoietin-1 Expression in Folic Acid-Induced Nephrotoxicity in Mice.
D. A. Long, A. S. Woolf, T. Suda, and H. T. Yuan (2001)
J. Am. Soc. Nephrol. 12, 2721-2731
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Increased Tie2 Expression, Enhanced Response to Angiopoietin-1, and Dysregulated Angiopoietin-2 Expression in Hemangioma-Derived Endothelial Cells.
Y. Yu, J. Varughese, L. F. Brown, J. B. Mulliken, and J. Bischoff (2001)
Am. J. Pathol. 159, 2271-2280
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Angiogenesis and Remodeling of Airway Vasculature in Chronic Inflammation.
D. M. MCDONALD (2001)
Am. J. Respir. Crit. Care Med. 164, S39-45
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Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1{alpha}.
D. A. Elson, G. Thurston, L. E. Huang, D. G. Ginzinger, D. M. McDonald, R. S. Johnson, and J. M. Arbeit (2001)
Genes & Dev. 15, 2520-2532
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