EGFL7 ligates αvβ3 integrin to enhance vessel formation

Iva Nikolić, Nevenka Dudvarski Stanković, Frank Bicker, Jeannette Meister, Helene Braun, Khader Awwad, Jan Baumgart, Kirsten Simon, Serge C. Thal, Chinmoy Patra, Patrick N. Harter, Karl H. Plate, Felix B. Engel, Stefanie Dimmeler, Johannes A. Eble, Michel Mittelbronn, Michael K. Schäfer, Benno Jungblut, Emmanouil Chavakis, Ingrid FlemingMirko H.H. Schmidt*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)

Abstract

Angiogenesis, defined as blood vessel formation from a preexisting vasculature, is governed by multiple signal cascades including integrin receptors, in particular integrin αVβ3. Here we identify the endothelial cell (EC)-secreted factor epidermal growth factorlike protein 7 (EGFL7) as a novel specific ligand of integrin α Vβ3, thus providing mechanistic insight into its proangiogenic actions in vitro and in vivo. Specifically, EGFL7 attaches to the extracellular matrix and by its interaction with integrin α Vβ3 increases the motility of EC, which allows EC to move on a sticky underground during vessel remodeling. We provide evidence that the deregulation of EGFL7 in zebrafish embryos leads to a severe integrin-dependentmalformation of the caudal venous plexus, pointing toward the significance of EGFL7 in vessel development. In biopsy specimens of patients with neurologic diseases, vascular EGFL7 expression rose with increasing EC proliferation. Further, EGFL7 became upregulated in vessels of the stroke penumbra using a mouse model of reversible middle cerebral artery occlusion. Our data suggest that EGFL7 expression depends on the remodeling state of the existing vasculature rather than on the phenotype of neurologic disease analyzed. In sum, our work sheds a novel light on the molecular mechanism EGFL7 engages to govern physiological and pathological angiogenesis.

Original languageEnglish
Pages (from-to)3041-3050
Number of pages10
JournalBlood
Volume121
Issue number15
DOIs
Publication statusPublished - 11 Apr 2013
Externally publishedYes

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