Lymphangiogenesis-independent resolution of experimental edema
Lymphangiogenesis-independent resolution of experimental edema
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DOI：
10.1152/ajpheart.00008.2010
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发表时间：
2010-07-01
影响因子：
4.8
通讯作者：
Goldman, Jeremy
中科院分区：
文献类型：
--
作者：
Ongstad, Emily L.;Bouta, Echoe M.;Goldman, Jeremy
Ongstad EL, Bouta EM, Roberts JE, Uzarski JS, Gibbs SE, Sabel MS, Cimmino VM, Roberts MA, Goldman J. Lymphangiogenesis-independent resolution of experimental edema. Am J Physiol Heart Circ Physiol 299: H46-H54, 2010. First published March 5, 2010; doi:10.1152/ajpheart.00008.2010.-Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis, and excess VEGF-C has been shown to be ameliorative for edema produced by lymphatic obstruction in experimental models. However, it has recently been shown that edema can resolve in the mouse tail even in the complete absence of capillary lymphangiogenesis when distal lymph fluid crosses the regenerating wound site interstitially. This finding has raised questions about the action of VEGF-C/VEGF receptor (VEGFR) signaling during the resolution of experimental edema. Here, the roles of VEGFR-2 and VEGFR-3 signaling in edema resolution were explored. It was found that edema resolved following neutralization of either VEGFR-2 or VEGFR-3 in the mouse tail skin, which inhibited lymphangiogenesis. Neutralization of either VEGFR-2 or VEGFR-3 reduced angiogenesis at the site of obstruction at day 10 (9.2 +/- 1.2% and 11.5 +/- 1.0% blood capillary coverage, respectively) relative to controls (14.3 +/- 1.5% blood capillary coverage). Combined VEGFR-2/-3 neutralization more strongly inhibited angiogenesis (6.9 +/- 1.5% blood capillary coverage), leading to a reduced wound repair of the lymphatic obstruction and extended edema in the tail skin. In contrast, improved tissue repair of the obstruction site increased edema resolution. Macrophages in the swollen tissue were excluded as contributing factors in the VEGFR-dependent extended edema. These results support a role for VEGFR-2/-3-combined signaling in the resolution of experimental edema that is lymphangiogenesis independent.
