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The FGF system positively regulates vascular integrity after ischemic injury
Author(s) -
Murakami Masahiro,
Moodie Karen L,
Zhuang Zhen W,
Ko In Kap,
Stan Radu V,
Simons Michael
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a636-b
Subject(s) - fibroblast growth factor , endothelial stem cell , ligation , angiogenesis , medicine , microbiology and biotechnology , biology , endocrinology , in vitro , biochemistry , receptor
Background The fibroblast growth factor (FGF) system plays significant roles in a wide variety of physiologic and pathologic conditions; however, early embryonic lethality of mice lacking either Fgfr‐1 or Fgfr‐2 precludes further studies focusing on FGF functions in the post‐developmental stage. Methods We generated a conditional transgenic mouse line that expresses truncated dominant‐negative FGFR1 (FGF‐R1DN) in the endothelium under the control of tetracycline regulated Tie2 promoter. The expression of FGF‐R1DN was induced in ten‐week old mice, and four weeks later hindlimb ischemia was produced by ligation of the right femoral artery. Results FGF‐R1DN mice demonstrated extensive toe/foot loss on the ischemic side of the leg following femoral artery ligation, accompanied by extensive apoptosis and concomitant reduction in tissue cGMP levels compared to control mice. Micro‐CT and stereo‐microscope analyses demonstrated vascular leakage and significant retention of contrast reagent throughout the ischemic region at the early stage of ischemic injury in FGF‐R1DN mice. Introduction of FGF‐R1DN adenovirus in rat femoral artery showed rearrangement of endothelial cell and disrupted cell junctions. Moreover, inhibition of FGF signaling in bovine aortic endothelial cells also showed displacement of VE‐cadherin and ZO‐1 from cell junctions, suggesting that the FGF signaling is required for the formation of endothelial junctions. Conclusion The FGF system appears to control maintenance of endothelial barrier function and vascular integrity, which plays an important role for tissue recovery from ischemic injury.