title: Temporal and spatial characterization of cellular constituents during neointimal hyperplasia after vascular injury: Potential contribution of bone-marrow-derived progenitors to arterial remodeling.
abstract: BACKGROUND
  Exuberant smooth muscle cells (SMCs) hyperplasia is the major cause of postangioplasty restenosis. We suggested that circulating smooth muscle progenitor cells might contribute to lesion formation after vascular injury.
  
  
  METHODS
  We extensively investigated the cellular constituents during neointimal formation after mechanical vascular injury.
  
  
  RESULTS
  A large wire was inserted into the mouse femoral artery, causing complete endothelial denudation and marked enlargement of the lumen with massive apoptosis of medial SMCs. At 2 h, the injured artery remained dilated with a thin media containing very few cells. A scanning electron microscopy showed fibrin and platelet deposition at the luminal side. One week after the injury, CD45-positive hematopoietic cells accumulated at the luminal side. Those CD45-positive cells gradually disappeared, whereas neointimal hyperplasia was formed with alpha-smooth muscle actin (SMA) positive cells. Bone marrow cells and peripheral mononuclear cells differentiated into alpha-SMA-positive cells in the presence of PDGF and basic FGF. Moreover, in bone marrow chimeric mice, bone-marrow-derived cells substantially contributed to neointimal hyperplasia after wire injury.
  
  
  CONCLUSIONS
  These results suggest that early accumulation of hematopoietic cells may play a role in the pathogenesis of SMC hyperplasia under certain circumstances.
authors.affiliation: Third Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shoji
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Daiju
authors.initials: D
authors.lastname: Fukuda
authors.forename: Kimie
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Koba
authors.forename: Eiichi
authors.initials: E
authors.lastname: Geshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000648:ultrastructure*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000199:Actins; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens