Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/36303
Title: VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation
Authors: Li, S
Dang, YY
Che, GOL
Kwan, YW
Chan, SW
Leung, GPH
Lee, SMY
Hoi, MPM
Keywords: Cardiovascular toxicity
Vascular insufficiency
Zebrafish model
Cardiovascular protective agents
Issue Date: 2014
Publisher: Academic Press
Source: Toxicology and applied pharmacology, 2014, v. 280, no. 3, p. 408-420 How to cite?
Journal: Toxicology and applied pharmacology 
Abstract: In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities.
URI: http://hdl.handle.net/10397/36303
ISSN: 0041-008X (print)
1096-0333 (online)
DOI: 10.1016/j.taap.2014.09.005
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

6
Last Week
0
Last month
Citations as of Feb 14, 2017

WEB OF SCIENCETM
Citations

5
Last Week
0
Last month
Citations as of Feb 17, 2017

Page view(s)

14
Last Week
1
Last month
Checked on Feb 19, 2017

Google ScholarTM

Check

Altmetric



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.