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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1962-1970.
Prepublished online as a Blood First Edition Paper on October 24, 2006; DOI 10.1182/blood-2005-10-038893.
Previous Article | Next Article 
Submitted October 21, 2005
Accepted October 13, 2006
Cooperation between VEGF and 3 integrin during cardiac vascular development
Sara M. Weis, Jeffrey N. Lindquist, Leo A. Barnes, Kimberly M. Lutu-Fuga, Jianhua Cui, Malcolm R. Wood, and David A. Cheresh*
Moores UCSD Cancer Center, University of California at San Diego, San Diego, CA
Core Microscopy Facility, The Scripps Research Institute, La Jolla, CA
* Corresponding author; email: dcheresh{at}ucsd.edu.
In the developing myocardium, vascular endothelial growth factor (VEGF)-dependent neovascularization occurs by division of existing vessels, a process that persists for several weeks following birth. During this remodeling phase, mRNA expression of 3 integrin in the heart decreases significantly as vessel maturation progresses. However, in male mice lacking 3, coronary capillaries fail to mature and continue to exhibit irregular endothelial thickness, endothelial protrusions into the lumen, and expanded cytoplasmic vacuoles. Surprisingly, this phenotype was not seen in female 3-null mice. Enhanced VEGF signaling contributes to the 3-null phenotype, since these vessels can be normalized by inhibitors of VEGF or Flk-1. Moreover, intravenous injection of VEGF induces a similar angiogenic phenotype in hearts of adult wildtype mice. These findings show a clear vascular phenotype in the hearts of mice lacking 3, and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF.

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