Role of shear-stress-induced VEGF expression in endothelial cell survival
View/ Open
Author
dela Paz, Nathaniel G.
Walshe, Tony E.
Leach, Lyndsay L.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1242/jcs.084301Metadata
Show full item recordCitation
Dela Paz, Nathaniel G., Tony E. Walshe, Lyndsay L. Leach, Magali Saint-Geniez, and Patricia A. D’Amore. 2012. “Role of Shear-Stress-Induced VEGF Expression in Endothelial Cell Survival.” Journal of Cell Science 125 (4) (February 15): 831–843. doi:10.1242/jcs.084301.Abstract
Vascular endothelial growth factor (VEGF) plays a crucial role in developmental and pathological angiogenesis. Expression of VEGF in quiescent adult tissue suggests a potential role in the maintenance of mature blood vessels. We demonstrate, using a Vegf–lacZ reporter mouse model, that VEGF is expressed by arterial but not by venous or capillary endothelial cells (ECs) in vivo. Using an in vitro model, we show that arterial shear stress of human umbilical vein ECs (HUVECs) decreases apoptosis and increases VEGF expression, which is mediated by the induction of Krüppel-like factor 2 (KLF2). Additionally, shear stress stimulates the expression of VEGF receptor 2 (VEGFR2) and is associated with its activation. Knockdown of VEGF in shear stressed HUVECs blocks the protective effect of shear stress, resulting in EC apoptosis equivalent to that in control ECs cultured under static conditions. Similarly, treatment of ECs subjected to arterial shear stress with the VEGF receptor tyrosine kinase inhibitor SU1498, or VEGFR2 neutralizing antiserum, led to increased apoptosis, demonstrating that the mechanoprotection from increased shear is mediated by VEGFR2. Taken together, these studies suggest that arterial flow induces VEGF–VEGFR2 autocrine–juxtacrine signaling, which is a previously unidentified mechanism for vascular EC survival in adult arterial blood vessels.Other Sources
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311927/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:34902776
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)
Comments made during the workflow steps
cat.complete