title: Angiogenesis occurs within the intimal proliferation that characterizes transplant coronary artery vasculopathy.
abstract: BACKGROUND
  Vascular remodeling is central to the development of transplant coronary artery vasculopathy (CAV). For remodeling to occur, a sustained blood and nutrient supply is essential. Here we report on the presence of angiogenesis within the neointima of coronary arteries from cardiac transplant recipients.
  
  
  METHODS
  Coronary arteries from 57 cardiac transplant recipients with CAV were analyzed. Immunocytochemistry with antibodies raised against endothelial cells (CD31, CD34, and vWF), vascular smooth muscle cells (SmA), and activated endothelial cells (MHC 2, P-SEL, E-SEL, and VCAM-1) was performed.
  
  
  RESULTS
  A total of 89% of patients had significant angiogenesis. These vessels appeared as endothelial lined channels and were present in a concentric circumferential pattern within the mid portion of the neointima. These new vessels were present at an interface between an area of intimal hyperplasia and below an area of fibrous regeneration. These 2 distinct zones were present in 64% of the cases, and were clearly demonstrated with an elastic van Gieson (EVG) stain and are distinctly different from that seen in native atherosclerosis. Endothelial activation markers were strongly expressed by the endothelial cells lining new vessels, suggesting that they are functional and may aid in the recruitment of inflammatory cells.
  
  
  CONCLUSIONS
  These data suggest that angiogenesis is present within the intima of CAV lesions and may contribute to the continued obliteration of the vessel lumen. The vessels appear to originate in the intima and may represent the location of the donor endothelium before transplantation. Inhibition of endothelial damage may provide therapeutic options to prevent the progression of CAV.
authors.affiliation: Pathology Department, Papworth Hospital NHS Trust, Papworth Everard, Cambridg, United Kingdom. carl.atkinson@papworth.nhs.uk
authors.forename: Carl
authors.initials: C
authors.lastname: Atkinson
authors.forename: Mark
authors.initials: M
authors.lastname: Southwood
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pitman
authors.forename: Colin
authors.initials: C
authors.lastname: Phillpotts
authors.forename: John
authors.initials: J
authors.lastname: Wallwork
authors.forename: Martin
authors.initials: M
authors.lastname: Goddard
mesh_terms: D000328:Adult; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D009389:Neovascularization, Pathologic / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D017539:Tunica Intima / Q000473:pathology