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J Thorac Cardiovasc Surg 2000;119:700-708
© 2000 The American Association for Thoracic Surgery

CARDIOTHORACIC TRANSPLANTATION

TRANSFORMING GROWTH FACTOR ß IN RELATION TO CARDIAC ALLOGRAFT VASCULOPATHY AFTER HEART TRANSPLANTATION

From the Cardiac Transplant Unit, Wythenshawe Hospital, University Department of Statistics,^a School of Biological Science,^b Manchester University, Manchester, United Kingdom.

Address for reprints: T. M. Aziz, FRCS, Division of Thoracic Surgery, Hairmyres Hospital, Eagleshame Rd, East Kilbride, Scotland, G75 8RG, United Kingdom.

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-ß) in the graft. Endomyocardial biopsy specimens were stained with antibodies for TGF-ß and CD+68, and a TGF-ß 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-ß₁ 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-ß 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-ß expression correlated with the degree of vasculopathy (r = 0.73, P < .0007) during the study period. Risks for vasculopathy were recipient homozygous TGF-ß 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-ß in cardiac biopsy specimens and the development of vasculopathy. TGF-ß in the cardiac allograft is related to its genotype and to the number of rejection episodes. Strategies to down-regulate TGF-ß production might improve the outcome of cardiac allografts.

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