Apoptotic cell death and genetic control in graft coronary artery disease in heart transplant.
OBJECTIVE
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.


CONCLUSIONS
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.
Di Stefano
S
S
Department of Cardiac Surgery, University Hospital,Valladolid, Spain. sdst@atenet.edu
Pardo
J
J
Panizo
A
A
Herreros
J
J
Tamayo
E
E
Florez
S
S
Fulquet
E
E
Echevarria
J R
JR
Carrascal
Y
Y
Fiz
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53