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Transforming growth factor beta in relation to cardiac allograft vasculopathy after heart transplantation
1Cardiac Transplant Unit, Wythenshawe Hospital, University Department of Statistics, Manchester University, Manchester, United Kingdom.
Insights
Transforming growth factor-beta (TGF-beta) expression in cardiac allografts is strongly associated with vasculopathy development. Down-regulating TGF-beta may improve heart transplant outcomes.
Area of Science:
- Cardiology
- Immunology
- Transplantation Science
Background:
- Cardiac allograft vasculopathy (CAV) is a common complication after heart transplantation.
- The role of cytokines, such as transforming growth factor-beta (TGF-beta), in CAV development is not well understood.
Purpose of the Study:
- To investigate the association between TGF-beta expression in cardiac allografts and the development of CAV.
- To identify risk factors for CAV in heart transplant recipients.
Main Methods:
- Retrospective study of 172 heart transplant recipients.
- Analysis of endomyocardial biopsy specimens for TGF-beta and CD+68 expression.
- Diagnosis of vasculopathy via angiography and grading of rejection.
- TGF-beta(1) genotyping using polymerase chain reaction.
Main Results:
- 52% prevalence of significant vasculopathy after a mean follow-up of 68 months.
- Higher TGF-beta staining scores correlated with more severe vasculopathy (P =.0001).
- Risk factors included recipient TGF-beta genotype, recurrent rejection, and donor characteristics.
Conclusions:
- A significant association exists between cardiac allograft TGF-beta expression and vasculopathy.
- TGF-beta expression is linked to allograft genotype and rejection episodes.
- Targeting TGF-beta production could potentially enhance cardiac allograft survival.
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.
Conclusion:
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.