期刊
NATURE MEDICINE
卷 15, 期 6, 页码 657-U145出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1985
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资金
- Goran Gustafsson Foundation
- Swedish Cancer Foundation [4422-B04O5XAB]
- Swedish Research Council [K2005-31X-15348-01A, 2006-13828-37891-37]
- Children's Cancer Foundation of Sweden [04/037]
- Lions Cancer Research Foundation in Uppsala
- Magnus Bergvall Foundation
- King Gustaf V's 80-Year Foundation
- Uppsala Foundation for Medical Research
- Crown Princess Margareta Foundation
- Edwin Jordan Foundation
- Karolinska Institute research grants
- Stiftelsen Synframjandets Forskningsfond
- St. Erik Eye Hospital Research Foundation
- Sigvard and Marianne Bernadotte Research Foundation for Children's Eye Care
Formation of new vessels in granulation tissue during wound healing has been assumed to occur solely through sprouting angiogenesis. In contrast, we show here that neovascularization can be accomplished by nonangiogenic expansion of preexisting vessels. Using neovascularization models based on the chick chorioallantoic membrane and the healing mouse cornea, we found that tissue tension generated by activated fibroblasts or myofibroblasts during wound contraction mediated and directed translocation of the vasculature. These mechanical forces pulled vessels from the preexisting vascular bed as vascular loops with functional circulation that expanded as an integral part of the growing granulation tissue through vessel enlargement and elongation. Blockade of vascular endothelial growth factor receptor-2 confirmed that biomechanical forces were sufficient to mediate the initial vascular growth independently of endothelial sprouting or proliferation. The neovascular network was further remodeled by splitting, sprouting and regression of individual vessels. This model explains the rapid appearance of large functional vessels in granulation tissue during wound healing.
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