Transforming growth factor β in relation to cardiac allograft vasculopathy after heart transplantation

Abstract

AbstractBackground: 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-β) in the graft. Endomyocardial biopsy specimens were stained with antibodies for TGF-β and CD+68, and a TGF-β 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-β1 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-β 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-β expression correlated with the degree of vasculopathy (r = 0.73, P < .0007) during the study period. Risks for vasculopathy were recipient homozygous TGF-β genotype, recurrent rejection, recipient history of ischemic heart disease, donor male sex, old donor age (years), and donor history of subarachnoid hemorrhage. Conclusion: A strong association exists between the expression of TGF-β in cardiac biopsy specimens and the development of vasculopathy. TGF-β in the cardiac allograft is related to its genotype and to the number of rejection episodes. Strategies to down-regulate TGF-β production might improve the outcome of cardiac allografts. (J Thorac Cardiovasc Surg 2000;119:700-8