Eph-B4 prevents venous adaptive remodeling in the adult arterial environment

Akihito Muto, Tai Yi, Kenneth D. Harrison, Alberto Dávalos, Tiffany T. Fancher, Kenneth R. Ziegler, Amanda Feigel, Yuka Kondo, Toshiya Nishibe, William C. Sessa, Alan Dardik

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36 Citations (Scopus)

Abstract

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4-Cav-1-mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.

Original languageEnglish
Pages (from-to)561-575
Number of pages15
JournalJournal of Experimental Medicine
Volume208
Issue number3
DOIs
Publication statusPublished - 14-03-2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Muto, A., Yi, T., Harrison, K. D., Dávalos, A., Fancher, T. T., Ziegler, K. R., Feigel, A., Kondo, Y., Nishibe, T., Sessa, W. C., & Dardik, A. (2011). Eph-B4 prevents venous adaptive remodeling in the adult arterial environment. Journal of Experimental Medicine, 208(3), 561-575. https://doi.org/10.1084/jem.20101854