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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 313302.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Critical function of Bmx/Etk in ischemia-mediated arteriogenesis and angiogenesis
Authors:He, Y.; Luo, Y.; Tang, S.; Rajantie, I.; Salven, P.; Heil, M.; Zhang, R.; Luo, D.; Li, X.; Chi, H.; Yu, J.; Carmeliet, P.; Schaper, W.; Sinusas, A. J.; Sessa, W. C.; Alitalo, K.; Min, W.
Date of Publication (YYYY-MM-DD):2006-09
Title of Journal:J Clin Invest
Journal Abbrev.:J Clin Invest
Issue / Number:9
Start Page:2344
End Page:2355
Audience:Not Specified
Abstract / Description:Bmx/Etk non-receptor tyrosine protein kinase has been implicated in endothelial cell migration and tube formation in vitro. However, the role of Bmx in vivo is not known. Bmx is highly induced in the vasculature of ischemic hind limbs. We used both mice with a genetic deletion of Bmx (Bmx-KO mice) and transgenic mice expressing a constitutively active form of Bmx under the endothelial Tie-2 enhancer/promoter (Bmx-SK-Tg mice) to study the role of Bmx in ischemia-mediated arteriogenesis/angiogenesis. In response to ischemia, Bmx-KO mice had markedly reduced, whereas Bmx-SK-Tg mice had enhanced, clinical recovery, limb perfusion, and ischemic reserve capacity when compared with nontransgenic control mice. The functional outcomes in these mice were correlated with ischemia-initiated arteriogenesis, capillary formation, and vessel maturation as well as Bmx-dependent expression/activation of TNF receptor 2- and VEGFR2-mediated (TNFR2/VEGFR2-mediated) angiogenic signaling in both hind limb and bone marrow. More importantly, results of bone marrow transplantation studies showed that Bmx in bone marrow-derived cells plays a critical role in the early phase of ischemic tissue remodeling. Our study provides the first demonstration to our knowledge that Bmx in endothelium and bone marrow plays a critical role in arteriogenesis/angiogenesis in vivo and suggests that Bmx may be a novel target for the treatment of vascular diseases such as coronary artery disease and peripheral arterial disease.
Free Keywords:Animals Hindlimb/*blood supply Humans Ischemia/*physiopathology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic *Neovascularization, Physiologic Protein-Tyrosine Kinases/genetics/*physiology
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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