title: Endothelial cell-dependent regulation of arteriogenesis.
abstract: BACKGROUND
  Arteriogenesis is the process of formation of arterial conduits. Its promotion is an attractive therapeutic strategy in occlusive atherosclerotic diseases. Despite the functional and clinical importance of arteriogenesis, the biology of the process is poorly understood. Synectin, a gene previously implicated in the regulation of vascular endothelial cell growth factor signaling, offers a unique opportunity to determine relative contributions of various cell types to arteriogenesis.
  
  
  OBJECTIVE
  We investigated the cell-autonomous effects of a synectin knockout in arterial morphogenesis.
  
  
  RESULTS
  A floxed synectin knockin mouse line was crossbred with endothelial-specific (Tie2, Cdh5, Pdgfb) and smooth muscle myosin heavy chain-specific Cre driver mouse lines to produce cell type-specific deletions. Ablation of synectin expression in endothelial, but not smooth muscle cells resulted in the presence of developmental arterial morphogenetic defects (smaller size of the arterial tree, reduced number of arterial branches and collaterals) and impaired arteriogenesis in adult mice.
  
  
  CONCLUSIONS
  Synectin modulates developmental and adult arteriogenesis in an endothelial cell-autonomous fashion. These findings show for the first time that endothelial cells are central to both developmental and adult arteriogenesis and provide a model for future studies of factors involved in this process.
authors.affiliation: From the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, New Haven, CT.
authors.forename: Filipa
authors.initials: F
authors.lastname: Moraes
authors.forename: Julie
authors.initials: J
authors.lastname: Paye
authors.forename: Feilim
authors.initials: F
authors.lastname: Mac Gabhann
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Lanahan
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005838:Genotype; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010641:Phenotype; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C115271:Gipc1 protein, mouse
keywords: arteries; arteriogenesis; collateral; endothelial cells; receptors; synectin; vascular endothelial growth factor
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