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Am J Physiol Heart Circ Physiol 291: H948-H956, 2006. First published April 14, 2006; doi:10.1152/ajpheart.00734.2005
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Chronic systemic delivery of angiopoietin-2 reveals a possible independent angiogenic effect

W. Bureau,1,2 P. Van Slyke,1,2 J. Jones,1 R. N. N. Han,3 Nicole L. Ward,6 D. J. Stewart,3,4,5 and D. J. Dumont1,2,4,5

1Molecular and Cellular Biology Research, Sunnybrook and Women’s Research Institute; 2Department of Medical Biophysics; 3Terrence Donnelly Heart Center, Division of Cardiology, St. Michael’s Hospital and the Department of Medicine; 4Heart and Stroke/Richard Lewar Centre of Excellence, Faculty of Medicine, University of Toronto; 5R. Samuel McLaughlin Centre for Molecular Medicine, Toronto, Ontario, Canada; and 6Departments of Dermatology and Neurosciences, School of Medicine; Case Western Reserve University, Cleveland, Ohio

Submitted 10 July 2005 ; accepted in final form 15 March 2006

Angiopoietin-2 has been implicated in the angiogenic response; however, this response has been tied to the expression of VEGF, and an independent angiogenic role has yet to be described. In this report, we detail the generation of transgenic mice that conditionally express angiopoietin-2 in the liver, resulting in sustained increases in circulating levels. These animals survive gestation and present with several vascular abnormalities, including an increase in the diameter of myocardial coronary vessels and a reduction in the density of endocardial vessels. In the lung, prominent increases in vessel diameter were observed. These vascular remodeling changes occurred in the absence of any apparent increase in VEGF expression. Our results illustrate that chronic systemic delivery of angiopoietin-2 induces angiogenesis in the absence of increased VEGF expression and that angiopoietin-2 promotes myocardial coronary vessel remodeling.

hemorrhage; lymphangiogenesis


Address for reprint requests and other correspondence: D. J. Dumont, Sunnybrook and Women’s Research Institute, 2075 Bayview Ave., Rm. S218, Toronto, ONT, Canada M4N 3M5 (e-mail: dan.dumont{at}sri.utoronto.ca)




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