Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells.

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Version: author
Serval ID
serval:BIB_74BB2DD3D866
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells.
Journal
Plos One
Author(s)
Tam J., Duda D.G., Perentes J.Y., Quadri R.S., Fukumura D., Jain R.K.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
4
Number
3
Pages
e4974
Language
english
Abstract
BACKGROUND: We investigated if new vessel formation in fat involves the contribution of local tissue-derived endothelial cells (i.e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO).
METHODOLOGY/PRINCIPAL FINDINGS: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by beta-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigated in fat tissue vessels after DIO using in vivo and ex vivo fluorescence microscopy. We investigated the roles of VEGF receptors 1 and 2 (VEGFR1/VEGFR2) by inducing DIO in mice and treating them with blocking monoclonal antibodies. We found only marginal (less than 1%) incorporation of BMDCs in fat vessels during DIO. When angiogenesis was inhibited by blocking VEGFR2 in mice with DIO, treated mice had significantly lower body weights than control animals. In contrast, blocking VEGFR1 had no discernable effect on the weight gain during DIO.
CONCLUSIONS/SIGNIFICANCE: Formation of new vessels in fat tissues during DIO is largely due to angiogenesis rather than de novo vasculogenesis. Antiangiogenic treatment by blockade of VEGFR2 but not VEGFR1 may limit adipose tissue expansion.
Keywords
Adipose Tissue/blood supply, Adipose Tissue/cytology, Animals, Body Weight, Bone Marrow Cells, Bone Marrow Transplantation, Cell Proliferation, Diet, Endothelial Cells/cytology, Mice, Mice, Transgenic, Neovascularization, Physiologic, Obesity/etiology, Vascular Endothelial Growth Factor Receptor-1/antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-1/physiology, Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-2/physiology
Pubmed
Open Access
Yes
Create date
01/07/2016 10:33
Last modification date
20/08/2019 14:32
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