Copyright © 2004 by the European Society of Cardiology.
Clinical research
Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation
a Department of Cardiovascular Medicine, Kaufman Center for Heart Failure and Transplantation, The Cleveland Clinic Foundation, F-25, 9500 Euclid Avenue, Cleveland, OH 44195, USA
b Heart Failure and Transplantation, Tulane University School of Medicine, New Orleans, LA, USA
c Department of Pathology, The Cleveland Clinic Foundation, Cleveland, OH, USA
d Allogen Laboratory, The Cleveland Clinic Foundation, Cleveland, OH, USA
e Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA
f London School of Hygiene and Tropical Medicine, University of London, London, UK
g Cardiothoracic Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA
* Corresponding author. Tel.: +1-216-444-2755; fax: +1-216-444-7155
E-mail address: Yamanim{at}ccf.org
Received 19 May 2003; revised 19 December 2003; accepted 15 January 2004
Abstract
Aims We tested the hypothesis that cardiac angiotensin II (Ang II) receptor gene transcription may predict the development of transplant coronary artery disease (TCAD) following heart transplantation.
Methods and results We examined the gene transcripts of Ang II type 1 (AT1R) and type 2 receptors (AT2R) in endomyocardial biopsy specimens from 50 heart transplant recipients. The progression of TCAD was measured as change in maximal intimal thickness (CMIT) and change in plaque volume (CPV) by intravascular ultrasound (IVUS) examinations from baseline to one year after transplantation. The development of transplant vasculopathy was defined as a CMIT of 
0.3 mm over one year. The level of AT1R mRNA was associated with that of AT2R in transplanted hearts (regression coefficient=1.77, 95% CI 0.85–2.89, 
). AT1R and AT2R gene transcripts were univariate predictors of CMIT (AT1R: regression coefficient 0.10, 95% CI 0.06–0.14, ; AT2R: regression coefficient 0.28, 95% CI 0.17–0.40, ) or CPV (AT1R: regression coefficient 0.41, 95% CI 0.17–0.65, ; AT2R: regression coefficient 1.25, 95% CI 0.49–2.01, 
). By one year, 21 (46%) transplant recipients showed evidence of transplant vasculopathy and the rest did not. The vasculopathic group demonstrated a higher level of expression of cardiac AT1R than the non-vasculopathic group (3.7±2.9 vs 1.6±1.7 folds; 
). The level of AT1R mRNA in transplanted heart was identified as a discriminator that predicted the development of transplant vasculopathy with a sensitivity of 75% and specificity of 83%.
Conclusions Cardiac Ang II receptor gene transcripts are associated with the progression of TCAD following heart transplantation. Only AT1R gene transcripts predicted the development of transplant vasculopathy in this preliminary study. These findings potentially support a role of Ang II receptors in the progression of TCAD following cardiac transplantation.
Key Words: Transplant coronary artery disease • Angiotensin II receptors • Intravascular ultrasound
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