title: The transcription factor HoxB5 stimulates vascular remodelling in a cytokine-dependent manner.
abstract: OBJECTIVE
  Proper blood vessel formation is essential in health and is often dysregulated in ischaemic diseases. Therefore, regulatory mechanisms that control angiogenesis and arteriogenesis are required to improve treatment of ischaemic diseases. The aim of this study was to investigate the role of homeobox transcription factor HoxB5 overexpression during revascularization in ischaemic disease.
  
  
  RESULTS
  To assess the effect of HoxB5 overexpression on blood vessel formation in vivo, we subjected C57BL/6 mice to femoral artery ligation with local intramuscular injection of HoxB5 or green fluorescent protein control adenoviral vectors. Laser Doppler perfusion imaging revealed that HoxB5 enhanced perfusion restoration in mice and immunohistochemistry analysis revealed increased capillary density. To identify a potential mechanism of HoxB5 in blood vessel formation, a 'proteome-profiler' array was performed. HoxB5 overexpression in endothelial cells increased the expression of pro-inflammatory molecules such as monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in vitro and in vivo. Functionally, HoxB5 enhanced monocyte as well as endothelial cell migration in vitro and increased leucocyte infiltration into ischaemic tissues. HoxB5-induced migration of monocytes was antagonized by the presence of an MCP-1 blocking antibody.
  
  
  CONCLUSIONS
  Our data suggest that overexpression of HoxB5 enhances blood vessel perfusion in vivo by up-regulation of MCP-1 and IL-6 as well as in enhanced leucocyte infiltration and blood vessel remodelling.
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fessner
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Esser
authors.forename: Franziska
authors.initials: F
authors.lastname: Bluhm
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grundmann
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001783:Blood Flow Velocity; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006614:Hindlimb; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007511:Ischemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012039:Regional Blood Flow; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C489126:HOXB5 protein, human; D018398:Homeodomain Proteins; D018836:Inflammation Mediators
keywords: Angio-/arteriogenesis; Gene expression; Inflammation; Ischaemia