Stimulation of Eph-B4 prevents adaptive remodeling and preserves venous identity when veins are surgically placed into an arterial environment

Abeles

Abulrob

Ackah

Adams

Akihito Muto

Alan Dardik

Alberto Dávalos

Alexander

Amanda Feigel

Bucci

Cohen

Conte

Couet

Dardik

Desai

Erber

Fernández-Hernando

Foubert

Fulton

García-Cardeña

Gerety

Gratton

Kenneth D. Harrison

Kenneth R. Ziegler

Khot

Kibbe

Kudo

Lajoie

Loftus

Mann

Mayr

Murata

Nicklin

Noren

Nystrom

Owens

Rizzo

Rudic

Shin

Stabila

Steinle

Szilagyi

Tai Yi

Tawara

Tiffany T. Fancher

Toshiya Nishibe

Veith

Vihanto

Wang

William C. Sessa

Yamamoto

Yuka Kondo

English

PubMed

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.</jats:p

Crossref

The Journal of Experimental Medicine

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

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3058579

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

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