Article
- The EMBO Journal (2008) 27, 522 - 534
- doi:10.1038/sj.emboj.7601982
Published online: 17 January 2008
Subject Category:
Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis
Hiroyasu Kidoya1, Masaya Ueno1, Yoshihiro Yamada1, Naoki Mochizuki2, Mitsugu Nakata3, Takashi Yano3, Ryo Fujii4 and Nobuyuki Takakura1
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
- Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, Japan
- Pharmaceutical Research Laboratories 1, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Yodogawa, Osaka, Japan
- Frontier Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Tsukuba-shi, Ibaraki, Japan
Correspondence to:
Nobuyuki Takakura, Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: +81 6 6879 8316; Fax: +81 6 6879 8314; E-mail: ntakaku@biken.osaka-u.ac.jp
Received 19 April 2007; Accepted 18 December 2007
Abstract
Blood vessels change their caliber to adapt to the demands of tissues or organs for oxygen and nutrients. This event is mainly organized at the capillary level and requires a size-sensing mechanism. However, the molecular regulatory mechanism involved in caliber size modification in blood vessels is not clear. Here we show that apelin, a protein secreted from endothelial cells under the activation of Tie2 receptor tyrosine kinase on endothelial cells, plays a role in the regulation of caliber size of blood vessel through its cognate receptor APJ, which is expressed on endothelial cells. During early embryogenesis, APJ is expressed on endothelial cells of the new blood vessels sprouted from the dorsal aorta, but not on pre-existing endothelial cells of the dorsal aorta. Apelin-deficient mice showed narrow blood vessels in intersomitic vessels during embryogenesis. Apelin enhanced endothelial cell proliferation in the presence of vascular endothelial growth factor and promoted cell-to-cell aggregation. These results indicated that the apelin/APJ system is involved in the regulation of blood vessel diameter during angiogenesis.
Keywords:
- angiogenesis,
- angiopoietin-1,
- apelin,
- APJ,
- lumen size
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