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Notch regulates the angiogenic response via induction of VEGFR-1

Yasuhiro Funahashi1,2 email, Carrie J Shawber1 email, Marina Vorontchikhina1 email, Anshula Sharma1 email, Hasina H Outtz1 email and Jan Kitajewski1 email

Pathology, Obstetrics and Gynecology, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA

Tsukuba Research Laboratories, Eisai Co, Ltd, Ibaraki, Japan

author email corresponding author email

Journal of Angiogenesis Research 2010, 2:3doi:10.1186/2040-2384-2-3

Published: 26 January 2010

Abstract

Notch is a critical regulator of angiogenesis and arterial specification. We show that ectopic expression of activated Notch1 induces endothelial morphogenesis in human umbilical vein endothelial cells (HUVEC) in a VEGFR-1-dependent manner. Notch1-mediated upregulation of VEGFR-1 in HUVEC increased their responsiveness to the VEGFR-1 specific ligand, Placental Growth Factor (PlGF). In mice and human endothelial cells, inhibition of Notch signaling resulted in decreased VEGFR-1 expression during VEGF-A-induced neovascularization. In summary, we show that Notch1 plays a role in endothelial cells by regulating VEGFR-1, a function that may be important for physiological and pathological angiogenesis.


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