title: Contribution of proliferating leukocytes to phenotypic change in smooth muscle cells during the development of coronary arteriosclerosis in transplanted hearts.
abstract: BACKGROUND
  It is well known that coronary arteriosclerosis after heart transplantation is concentric and rich in smooth muscle cells (SMCs); however, the role played by rejection in the intimal thickening caused by SMCs in coronary arteriosclerosis remains unclear. In this study, we examined the process of intimal hyperplasia caused by SMCs and evaluated the relationship between the differentiation state of SMCs and local inflammation caused by rejection.
  
  
  METHODS
  Lewis rat hearts were heterotopically transplanted into F344 rats (allotransplantation group) or other Lewis rats (isotransplantation group). Cyclosporin A (5 mg/kg/day) was injected intramuscularly for 20 days after transplantation in both groups. The transplanted hearts were examined immunohistochemically using several monoclonal antibodies; namely, HHF-35, CGA7, vimentin, alpha-actin, HIS36, R73 and proliferating cell nuclear antigen (PCNA). To evaluate the degree of local immunological response caused by rejection, the anti-PCNA antibody was used. To reveal the subtypes of proliferating cells in the thickened intima, HIS36 and R73 antibodies were used.
  
  
  RESULTS
  In the allotransplantation group, SMCs in the media began to undergo a phenotypic change toward a poorly differentiated state 30 days after transplantation. Intimal hyperplasia was observed 60 days after transplantation, the thickened intima being composed mainly of dedifferentiated SMCs with abundant PCNA(+), most of which were macrophages and T cells. The state of differentiation of SMCs in the thickened intima 90 days after transplantation varied from a dedifferentiated to a highly differentiated state. These changes were strongly correlated with the expression of PCNA.
  
  
  CONCLUSIONS
  The expression of PCNA was strongly correlated with the differentiation state of SMCs. Thus, local inflammation caused by rejection may play an important role in the initiation of phenotypic change in SMCs.
authors.affiliation: First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Shirasawa
authors.forename: K
authors.initials: K
authors.lastname: Hamano
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
authors.forename: A
authors.initials: A
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Esato
mesh_terms: D000818:Animals; D002455:Cell Division; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D006084:Graft Rejection; D016027:Heart Transplantation / Q000009:adverse effects*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018809:Proliferating Cell Nuclear Antigen