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Critical function of Bmx/Etk in inflammatory arteriogenesis/angiogenesis
Author(s) -
He Yun,
Luo Yan,
Min Wang
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.20.5.a1078-b
Subject(s) - arteriogenesis , angiogenesis , vasculogenesis , medicine , vascular endothelial growth factor , bone marrow , cancer research , immunology , progenitor cell , microbiology and biotechnology , biology , stem cell , vegf receptors
Bmx (bone marrow tyrosine kinase in chromosome‐X) (also named Etk, endothelial/epithelial tyrosine kinase) has been implicated in endothelial cell migration and tube formation in vitro. However, the role of Bmx in vivo is not known. In the present study, we use an endothelial‐specific transgenic mice expressing a constitutively active form of Bmx containing the SH2 and the kinase domains by a Tie‐2 enhancer/promoter (Bmx‐SK‐Tg) to demonstrate a critical role of Bmx in inflammatory arteriogenesis/angiogenesis. Bmx was highly induced in ischemic hindlimb after femoral artery ligation, a common used inflammatory angiogenesis model. In response to femoral ligation, Bmx‐SK‐Tg mice had enhanced clinical recovery, limb perfusion and ischemic reserve capacity compared to C57BL6 mice. Microfil casting showed that Bmx‐SK‐Tg mice had increased ischemia initiated arteriogenesis in the upper limb. Histology analyses indicate that Bmx‐SK‐Tg increased, capillary formation and vessel maturation in the ischemia limb compared to C57BL6 mice. Gene profiling suggests that proinflammatory cytokines TNF and its TNFR2, proangiogenic factors angiopoetin and its receptor Tie‐2, VEGF and its receptor VEGFR2, and pericyte recruiting factors PDGF and its receptor PDGFR were significantly enhanced on day 7 in response to ischemia in Bmx‐SK‐Tg mice. Bmx and Bmx‐SK were detected in bone morrow, and Bmx‐SK‐Tg increased endothelial progenitor cell (EPC) mobilization in response to hindlimb ischemia. Collectively, our data suggest that Bmx plays a critical role in mediating inflammatory arteriogenesis/angiogenesis in vivo.