Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation.
OBJECTIVE
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.


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 > or = 0.3 mm over one year. The level of AT(1)R mRNA was associated with that of AT2R in transplanted hearts (regression coefficient=1.77, 95% CI 0.85-2.89, p<0.0001). AT1R and AT2R gene transcripts were univariate predictors of CMIT (AT1R: regression coefficient 0.10, 95% CI 0.06-0.14, p<0.0001; AT2R: regression coefficient 0.28, 95% CI 0.17-0.40, p<0.0001 ) or CPV (AT1R: regression coefficient 0.41, 95% CI 0.17-0.65, p<0.0001 ; AT2R: regression coefficient 1.25, 95% CI 0.49-2.01, p=0.002 ). 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; p=0.006). The level of AT(1)R 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.
Yousufuddin
Mohammed
M
Department of Cardiovascular Medicine, Kaufman Center for Heart Failure and Transplantation, The Cleveland Clinic Foundation, F-25, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Haji
Showkat
S
Starling
Randall C
RC
Tuzcu
E Murat
EM
Ratliff
Norman B
NB
Cook
Daniel J
DJ
Abdo
Ashraf
A
Saad
Yasser
Y
Karnik
Sadashiva S
SS
Wang
Duolao
D
McCarthy
Patrick M
PM
Young
James B
JB
Yamani
Mohamad H
MH
D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017539:Tunica Intima / Q000473:pathology
D015415:Biomarkers; D012333:RNA, Messenger; D011945:Receptors, Angiotensin