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Published on: May 14, 2013
Apoptotic cell death and genetic control in graft coronary artery disease in heart transplant
S Di Stefano1, J Pardo, A Panizo
1Department of Cardiac Surgery, University Hospital,Valladolid, Spain. sdst@atenet.edu
Insights
Heart transplant patients with coronary artery disease show significant apoptotic cardiomyocytes. This programmed cell death is a constant finding, but not linked to genetic mechanisms in this study.
Area of Science:
- Cardiology
- Immunology
- Cell Biology
Background:
- Graft coronary artery disease significantly limits long-term survival after heart transplantation.
- Apoptosis, or programmed cell death, plays a role in various biological processes.
Purpose of the Study:
- To analyze apoptotic cell lesions in heart transplant recipients diagnosed with coronary artery disease.
Main Methods:
- Endomyocardial biopsies from 148 heart transplant patients (1984-1996) were analyzed for apoptosis using the TUNEL technique.
- Immunohistochemistry was performed for c-myc, p53, and bcl-2, with results compared to a control group.
Main Results:
- All 30 patients with coronary artery disease exhibited apoptotic cardiomyocytes, with varying degrees of severity.
- The control group showed only mild apoptosis in 8 patients, a statistically significant difference (p<0.0001).
- No significant expression of c-myc, p53, or bcl-2 oncoproteins was observed in either group.
Conclusions:
- Myocardial apoptosis is a consistent finding in heart transplant patients who develop coronary artery disease.
- The study did not find a correlation between the apoptotic process and genetic mechanisms in this patient cohort.
Aim:
Apoptosis is a type of programmed cell death whereby, immunologic, genetic and biochemical mechanisms are involved in its control. On the other hand, graft coronary artery disease is the most important restrictive factor for the long-term survival of heart transplantation. The purpose of this study is to analyse both apoptotic cell lesions in transplanted patients that present coronary artery disease.
Methods:
From August 1984 until December 1996, 148 heart transplants were carried out in the Clínica Universitaria de Navarra. In 102 patients, annual coronary angiography was performed, reaching a diagnosis of coronary artery disease in 30 patients. Study of apoptotic cell death was done in the tissue of endomyocardial biopsies on all patients by means of the TUNEL technique. Procedures of immunohistochemistry with antibodies antic-myc, p53 and bcl-2 were carried out and results were compared with a control group of 30 patients with homogeneous characteristics.
Results:
All patients with coronary artery disease showed apoptotic cardiomyocytes, 13 patients to a mild degree, 14 to a moderate degree and 3 to a severe degree, while in the control group apoptosis was found only to a mild degree in 8 patients, obtaining a very significant statistical difference (p<0.0001). The expression of analysed oncoproteins was null in the 2 groups.
Conclusion:
Myocardial apoptosis is a constant finding in transplanted patients with coronary artery disease. We have not seen any correlation between the apoptotic process and genetic mechanisms.
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