title: Absence of p53 leads to accelerated neointimal hyperplasia after vascular injury.
abstract: OBJECTIVE
  It has been suggested that deregulated expression of the tumor suppressor protein p53 may play a role in the pathogenesis of occlusive vascular remodeling. However, the role of p53 in cell proliferation and apoptosis in vascular lesions has been controversial.
  
  
  RESULTS
  We tested the potential involvement of p53-mediated molecular signaling in lesion formation using a mouse model of vascular injury that may resemble balloon angioplasty. A large wire was inserted into the femoral artery of p53+/+ and p53-/- mice. There was no significant difference in the occurrence of rapid-onset apoptosis, that is, 4 hours after injury. At 2 weeks, the number of proliferating cells in the lesion of p53-/- mice was significantly higher than that observed in p53+/+ mice. The frequency of apoptotic cells was significantly lower in p53-/- mice than in p53+/+ mice. At 4 weeks, the neointimal hyperplasia of p53-/- mice was greater than that of p53+/+ mice. There was no significant difference in the frequency of apoptosis in the lesions.
  
  
  CONCLUSIONS
  These results indicate a crucial role of p53 in pathological vascular remodeling after mechanical injury and provide the basis for the development of new therapies targeting p53 for a prophylactic treatment of vascular diseases.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan. msata-circ@umin.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Kimie
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics; D016158:Genes, p53 / Q000502:physiology; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology*
chemical_list: D000199:Actins; D016159:Tumor Suppressor Protein p53