title: Vascular cell adhesion molecule-1 up-regulation and phenotypic modulation of vascular smooth muscle cells predate mononuclear infiltration in transplant arteriopathy.
abstract: OBJECTIVE
  Expression of embryonic myosin heavy chain isoforms and vascular cell adhesion molecule-1 by neointimal vascular smooth muscle cells are independent indicators of atherosclerotic plaque development in both human beings and experimental animal models. We examined the chronologic change in smooth muscle cell myosin heavy chain isoforms, vascular cell adhesion molecule-1 expression, and mononuclear cell infiltration in a carotid arterial transplant model to ascertain whether similar phenotypic changes would occur in transplant arteriopathy.
  
  
  METHODS
  Transplanted rabbit carotid arteries were examined at 7, 14, 21, and 35 days (n = 5, 7, 6, and 5, respectively). Lesion progression and the prevalence of smooth muscle cell myosin heavy chain isoforms, T-lymphocytes, macrophages, and vascular cell adhesion molecule-1 expression were evaluated immunohistochemically by computerized image analysis.
  
  
  RESULTS
  In this carotid arterial transplant model, the intima/media area ratio increased significantly by 35 days (P =.01) as cell density decreased (P =.01), suggesting extracellular matrix elaboration. Intimal smooth muscle cells expressing embryonic phenotypes were seen as early as 7 days, a phenotypic change that predated mononuclear cell infiltration of the graft by at least 7 days. By 35 days, up to 70% of intimal smooth muscle cells expressed the embryonic phenotype, coinciding with the transition from inflammatory to chronic lesions. Although, in early lesions, vascular cell adhesion molecule-1 was identified on luminal endothelium overlying mononuclear infiltrates, in advanced lesions vascular cell adhesion molecule-1 was identified primarily on intimal vascular smooth muscle cells.
  
  
  CONCLUSIONS
  Overall, these vascular smooth muscle cell changes mark important early events in transplant arteriopathy that may not be ameliorated by immunosuppressive regimens in routine use.
authors.affiliation: Department of Cardiovascular Surgery, Tohoku University, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sai
authors.forename: A
authors.initials: A
authors.lastname: Iwata
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: M D
authors.initials: MD
authors.lastname: Allen
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002339:Carotid Arteries / Q000166:cytology* / Q000637:transplantation*; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000502:physiology*; D010641:Phenotype; D011183:Postoperative Complications / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020033:Protein Isoforms; D011817:Rabbits; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000166:cytology* / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D019010:Vascular Cell Adhesion Molecule-1; D018995:Myosin Heavy Chains