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

Mohammed Yousufuddin, Showkat Haji, Randall C. Starling, E. Murat Tuzcu, Norman B. Ratliff, Daniel J. Cook, Ashraf Abdo, Yasser Saad, Sadashiva S. Karnik, Duolao Wang, Patrick M. McCarthy, James B. Young, Mohamad H. Yamani

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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, 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.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalEuropean Heart Journal
Volume25
Issue number5
DOIs
StatePublished - Mar 1 2004

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Angiotensin Receptors
Heart Transplantation
Coronary Artery Disease
Transplants
Tunica Intima
Genes
Messenger RNA
Angiotensin II
Transplantation
Biopsy
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation. / Yousufuddin, Mohammed; Haji, Showkat; Starling, Randall C.; Tuzcu, E. Murat; Ratliff, Norman B.; Cook, Daniel J.; Abdo, Ashraf; Saad, Yasser; Karnik, Sadashiva S.; Wang, Duolao; McCarthy, Patrick M.; Young, James B.; Yamani, Mohamad H.

In: European Heart Journal, Vol. 25, No. 5, 01.03.2004, p. 377-385.

Research output: Contribution to journalArticle

Yousufuddin, M, Haji, S, Starling, RC, Tuzcu, EM, Ratliff, NB, Cook, DJ, Abdo, A, Saad, Y, Karnik, SS, Wang, D, McCarthy, PM, Young, JB & Yamani, MH 2004, 'Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation', European Heart Journal, vol. 25, no. 5, pp. 377-385. https://doi.org/10.1016/j.ehj.2004.01.005
Yousufuddin, Mohammed ; Haji, Showkat ; Starling, Randall C. ; Tuzcu, E. Murat ; Ratliff, Norman B. ; Cook, Daniel J. ; Abdo, Ashraf ; Saad, Yasser ; Karnik, Sadashiva S. ; Wang, Duolao ; McCarthy, Patrick M. ; Young, James B. ; Yamani, Mohamad H. / Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation. In: European Heart Journal. 2004 ; Vol. 25, No. 5. pp. 377-385.
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title = "Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation",
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, 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.",
author = "Mohammed Yousufuddin and Showkat Haji and Starling, {Randall C.} and Tuzcu, {E. Murat} and Ratliff, {Norman B.} and Cook, {Daniel J.} and Ashraf Abdo and Yasser Saad and Karnik, {Sadashiva S.} and Duolao Wang and McCarthy, {Patrick M.} and Young, {James B.} and Yamani, {Mohamad H.}",
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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 - 2004/3/1

Y1 - 2004/3/1

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.

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