Please use this identifier to cite or link to this item: https://doi.org/10.1161/01.RES.0000185327.45463.A8
Title: Novel role of lactosylceramide in vascular endothelial growth factor-mediated angiogenesis in human endothelial cells
Authors: Rajesh, M. 
Kolmakova, A.
Chatterjee, S. 
Keywords: Angiogenesis
Lactosylceramide
Platelet endothelial cell adhesion molecule-1
Vascular endothelial growth factor
Issue Date: 14-Oct-2005
Citation: Rajesh, M., Kolmakova, A., Chatterjee, S. (2005-10-14). Novel role of lactosylceramide in vascular endothelial growth factor-mediated angiogenesis in human endothelial cells. Circulation Research 97 (8) : 796-804. ScholarBank@NUS Repository. https://doi.org/10.1161/01.RES.0000185327.45463.A8
Abstract: Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis associated with coronary heart disease, vascular complications in diabetes, inflammatory vascular diseases, and tumor metastasis. The mechanism of VEGF-driven angiogenesis involving glycosphingolipids such as lactosylceramide (LacCer), however, is not known. To demonstrate the involvement of LacCer in VEGF-induced angiogenesis, we used small interfering RNA (siRNA)-mediated silencing of LacCer synthase expression (GalT-V) in human umbilical vein endothelial cells. This gene silencing markedly inhibited VEGF-induced platelet endothelial cell adhesion molecule-1 (PECAM-1) expression and angiogenesis. Second, we used D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of LacCer synthase and glucosylceramide synthase, that significantly mitigated VEGF-induced PECAM-1 expression and angiogenesis. Interestingly, these phenotypic changes were reversed by LacCer but not by structurally related compounds such as glucosylceramide, digalactosylceramide, and ceramide. In a human mesothelioma cell line (REN) that lacks the endogenous expression of PECAM-1, VEGF/LacCer failed to stimulate PECAM-1 expression and tube formation/angiogenesis. In REN cells expressing human PECAM-1 gene/protein, however, both VEGF and LacCer-induced PECAM-1 protein expression and tube formation /angiogenesis. In fact, VEGF-induced but not LacCer-induced angiogenesis was mitigated by SU-1498, a VEGF receptor tyrosine kinase inhibitor. Also, VEGF/LacCer induced PECAM-1 expression and angiogenesis was mitigated by protein kinase C and phospholipase A 2 inhibitors. These results indicate that LacCer generated in VEGF-treated endothelial cells may serve as an important signaling molecule for PECAM-1 expression and in angiogenesis. This finding and the reagents developed in our report may be useful as anti-angiogenic drugs for further studies in vitro and in vivo. © 2005 American Heart Association, Inc.
Source Title: Circulation Research
URI: http://scholarbank.nus.edu.sg/handle/10635/107736
ISSN: 00097330
DOI: 10.1161/01.RES.0000185327.45463.A8
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

39
checked on Jun 16, 2018

WEB OF SCIENCETM
Citations

37
checked on May 28, 2018

Page view(s)

57
checked on Jun 1, 2018

Google ScholarTM

Check

Altmetric


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