title: Neointimal smooth muscle cells in human cardiac allograft coronary artery vasculopathy are of donor origin.
abstract: BACKGROUND
  Transplant coronary artery vasculopathy (CAV) is a fibro-proliferative process that leads to lumen occlusion and cardiac failure. Current theories suggest that the process evolves over time in response to inflammation and proliferation of donor derived medial smooth muscle cells (SMC). Animal models of cardiac transplantation have suggested that the neointima is formed by recipient derived circulating progenitor cells. The aim of this investigation is to determine the origin of the neointimal SMC within epicardial coronary arteries from human cardiac allografts by using sex mis-matched recipients and donors, and a Y specific chromosome probe.
  
  
  METHODS
  Coronary arteries from 14 patients previously assessed histologically to have CAV were analyzed-eight male recipients of female donor organs, 2 female-to-female, and 4 male-to-male transplants. A double immunocytochemistry and in-situ hybridization technique using a Y chromosome DNA probe and either antibodies to smooth muscle actin or Ham-56 a macrophage marker were employed.
  
  
  RESULTS
  No Y chromosome bodies could be identified in the female-to-female allografts. In the 4 male donor and male recipient cases, cells positive for the Y chromosome probe were identified. In sex mis-matched transplants, female to male, inflammatory cells marked with Ham-56 were also positive for Y chromosome probe. Flattened cells positive for Y chromosome were observed just beneath the endothelial surface. When double stained, these were identified as infiltrating macrophages. No double staining smooth muscle cells and Y chromosome positive cells could be identified within the neointima.
  
  
  CONCLUSIONS
  This study confirms the source of SMC of the neointima of CAV lesions from epicardial coronary arteries to be of donor origin. In contrast to animal models, circulating progenitor cells do not appear to play a role within the neointima of human transplant CAV.
authors.affiliation: Department of Pathology, Papworth NHS Trust Hospital, Cambridge, UK. carl.atkinson@papworth.nhs.uk
authors.forename: Carl
authors.initials: C
authors.lastname: Atkinson
authors.forename: Joanne
authors.initials: J
authors.lastname: Horsley
authors.forename: Susan
authors.initials: S
authors.lastname: Rhind-Tutt
authors.forename: Susan
authors.initials: S
authors.lastname: Charman
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Phillpotts
authors.forename: John
authors.initials: J
authors.lastname: Wallwork
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Goddard
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement; D041322:Chromosomes, Human, Y; D003324:Coronary Artery Disease / Q000209:etiology* / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D017539:Tunica Intima / Q000166:cytology*