title: Transforming growth factor beta in relation to cardiac allograft vasculopathy after heart transplantation.
abstract: BACKGROUND
  Cardiac allograft vasculopathy is a frequent sequel to cardiac transplantation, but the role of cytokines on the subsequent development of vasculopathy is still largely unknown.
  
  
  METHODS
  We retrospectively studied 172 heart transplant recipients to investigate the relationship between the development of vasculopathy and various factors including the presence of transforming growth factor (TGF-beta) in the graft. Endomyocardial biopsy specimens were stained with antibodies for TGF-beta and CD+68, and a TGF-beta staining score was derived. Vasculopathy was diagnosed by angiography and rejection was graded according to the International Society of Heart and Lung Transplantation classification. TGF-beta(1) genotype was determined by polymerase chain reaction analysis of DNA.
  
  
  RESULTS
  After a mean follow-up period of 68 +/- 32 months, the prevalence of significant vasculopathy was 52%. The TGF-beta staining score was higher in patients with more severe vasculopathy (95% confidence interval = 8.9-12.1) than in those who showed minimal or mild vasculopathy score changes of more than 7 (95% confidence interval = 3.4-5.1), P =.0001. TGF-beta expression correlated with the degree of vasculopathy (r = 0.73, P <.0007) during the study period. Risks for vasculopathy were recipient homozygous TGF-beta genotype, recurrent rejection, recipient history of ischemic heart disease, donor male sex, old donor age (years), and donor history of subarachnoid hemorrhage.
  
  
  CONCLUSIONS
  A strong association exists between the expression of TGF-beta in cardiac biopsy specimens and the development of vasculopathy. TGF-beta in the cardiac allograft is related to its genotype and to the number of rejection episodes. Strategies to down-regulate TGF-beta production might improve the outcome of cardiac allografts.
authors.affiliation: Cardiac Transplant Unit, Wythenshawe Hospital, University Department of Statistics, Manchester University, Manchester, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Aziz
authors.forename: P
authors.initials: P
authors.lastname: Hasleton
authors.forename: A W
authors.initials: AW
authors.lastname: Hann
authors.forename: N
authors.initials: N
authors.lastname: Yonan
authors.forename: A
authors.initials: A
authors.lastname: Deiraniya
authors.forename: I V
authors.initials: IV
authors.lastname: Hutchinson
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D004699:Endocardium / Q000473:pathology; D005260:Female; D005838:Genotype; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics
chemical_list: D016212:Transforming Growth Factor beta