TY - JOUR
T1 - Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation
AU - Yousufuddin, Mohammed
AU - Haji, Showkat
AU - Starling, Randall C.
AU - Tuzcu, E. Murat
AU - Ratliff, Norman B.
AU - Cook, Daniel J.
AU - Abdo, Ashraf
AU - Saad, Yasser
AU - Karnik, Sadashiva S.
AU - Wang, Duolao
AU - McCarthy, Patrick M.
AU - Young, James B.
AU - Yamani, Mohamad H.
PY - 2004/3
Y1 - 2004/3
N2 - 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, P < 0.0001). AT1R and AT2R gene transcripts were univariate predictors of CMIT (AT 1R: 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 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.
AB - 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, P < 0.0001). AT1R and AT2R gene transcripts were univariate predictors of CMIT (AT 1R: 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 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.
KW - Angiotensin II receptors
KW - Intravascular ultrasound
KW - Transplant coronary artery disease
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U2 - 10.1016/j.ehj.2004.01.005
DO - 10.1016/j.ehj.2004.01.005
M3 - Article
C2 - 15033249
AN - SCOPUS:12144287330
SN - 0195-668X
VL - 25
SP - 377
EP - 385
JO - European heart journal
JF - European heart journal
IS - 5
ER -