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Article

  • The EMBO Journal (2008) 27, 1658 - 1670
  • doi:10.1038/emboj.2008.103

Published online: 22 May 2008

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

Etienne Lelièvre1, Aleksander Hinek2, Florea Lupu3, Christelle Buquet1, Fabrice Soncin1 and Virginie Mattot1

  1. CNRS, UMR 8161, Institut de Biologie de Lille, Equipe labellisée 'La Ligue 2005', Université de Lille I, Université de Lille II, Institut Pasteur de Lille, Lille, France
  2. Hospital for Sick Children, University of Toronto Cardiovascular Program, Toronto, Ontario, Canada
  3. Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

Correspondence to:

Virginie Mattot, CNRS, UMR 8161, Institut de Biologie de Lille, 1 Rue Calmette, BP 447 59021, Lille cedex, France. Tel.: +33 3 2087 1118; Fax: +33 3 2087 1111; E-mail: virginie.mattot@ibl.fr

Received 15 January 2008; Accepted 28 April 2008

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.

  • Keywords:

    • egfl7,
    • elastogenesis,
    • lysyl oxidases,
    • VE-statin