Chronic systemic delivery of angiopoietin-2 reveals a possible independent angiogenic effect.
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.
Bureau
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Molecular and Cellular Biology Research, Sunnybrook and Women's Research Institute, 2075 Bayview Ave., Rm. S218, Toronto, ONT, Canada M4N 3M5.
Van Slyke
P
P
Jones
J
J
Han
R N N
RN
Ward
Nicole L
NL
Stewart
D J
DJ
Dumont
D J
DJ
D042702:Angiopoietin-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D005451:Fluorescein Angiography; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008208:Lymphatic System / Q000033:anatomy & histology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010766:Phosphorylation; D042787:Receptor, TIE-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2