Loading…

VE-statin/egfl7 regulates vascular elastogenesis by interacting with lysyl oxidases

We previously characterized VE‐statin/egfl7, a protein that is exclusively secreted by endothelial cells and modulates smooth muscle cell migration. Here, we show that VE‐statin/egfl7 is the first known natural negative regulator of vascular elastogenesis. Transgenic mice, expressing VE‐statin/egfl7...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2008-06, Vol.27 (12), p.1658-1670
Main Authors: Lelièvre, Etienne, Hinek, Aleksander, Lupu, Florea, Buquet, Christelle, Soncin, Fabrice, Mattot, Virginie
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We previously characterized VE‐statin/egfl7, a protein that is exclusively secreted by endothelial cells and modulates smooth muscle cell migration. Here, we show that VE‐statin/egfl7 is the first known natural negative regulator of vascular elastogenesis. Transgenic mice, expressing VE‐statin/egfl7 under the control of keratin‐14 promoter, showed an accumulation of VE‐statin/egfl7 in arterial walls where its presence correlated with an impaired organization of elastic fibres. In vitro , fibroblasts cultured in the presence of VE‐statin/egfl7 were unable to deposit elastic fibres due to a deficient conversion of soluble tropoelastin into insoluble mature elastin. VE‐statin/egfl7 interacts with the catalytic domain of lysyl oxidase (LOX) enzymes and, in endothelial cells, endogenous VE‐statin/egfl7 colocalizes with LoxL2 and inhibits elastic fibre deposition. In contrast, mature elastic fibres are abundantly deposited by endothelial cells that are prevented from producing endogenous VE‐statin/egfl7. We propose a model where VE‐statin/egfl7 produced by endothelial cells binds to the catalytic domains of enzymes of the LOX family in the vascular wall, thereby preventing the crosslink of tropoelastin molecules into mature elastin polymers and regulating vascular elastogenesis.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2008.103