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CLINICAL RESEARCH: CARDIAC TRANSPLANT AND ASSIST DEVICES

Angiotensin II receptors from peritransplantation through first-year post-transplantation and the risk of transplant coronary artery disease

Mohammed Yousufuddin, MD, MRCPE, MRCPI^*, Daniel J. Cook, PhD, Randall C. Starling, MD, MPH^*, Ashraf Abdo, MD, Philip Paul, MD, E. Murat Tuzcu, MD^*, Norman B. Ratliff, MD, Patrick M. McCarthy, MD, James B. Young, MD^* and Mohamad H. Yamani, MD^*,*

^* Department of Cardiovascular Medicine, USA
Allogen Laboratory, Cleveland, Ohio, USA
Department of Pathology, Cleveland, Ohio, USA
Cardiothoracic Surgery, Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Manuscript received September 9, 2003; revised manuscript received November 24, 2003, accepted November 25, 2003.

^* Reprint requests and correspondence: Dr. Mohamad H. Yamani, Cleveland Clinic Foundation, Cardiovascular Medicine, F25, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
yamanim{at}ccf.org

OBJECTIVES: We evaluated whether the angiotensin II (Ang II) receptors from perioperation through one-year post-transplantation predict the transplant coronary artery disease (TCAD) progression.

BACKGROUND: The role of Ang II receptors (type 1: AT₁R; type 2: AT₂R) in TCAD is uncertain.

METHODS: We investigated 28 heart donors and the corresponding recipients. The levels of AT₁R and AT₂R messenger ribonucleic acid (mRNA) were examined in lymphocytes from the donor spleen and in the donor heart at one-week and one-year posttransplantation to determine their association with the progression of TCAD, measured as changes in maximal intimal thickness (CMIT) and plaque volume (CPV) by intravascular ultrasound (IVUS) examinations.

RESULTS: The AT₁R mRNA in lymphocytes from the donor spleen (CMIT: r = 0.73, p < 0.0001; CPV: r = 0.69, p < 0.0001) and in the donor hearts at one-week (CMIT: r = 0.52, p = 0.005; CPV: r = 0.56, p = 0.002) and at one-year (CMIT: r = 0.63, p < 0.0001; CPV: r = 0.43, p = 0.004) post-transplantation along with AT₂R mRNA in the donor hearts at one-year post-transplantation (CMIT: r = 0.3, p < 0.0001; CPV: r = 0.53, p = 0.009) were univariate predictors, whereas AT₁R mRNA in lymphocytes and in the donor hearts at one-year post-transplantation proved to be multivariate predictors of the progression of TCAD.

CONCLUSIONS: These data suggest a role for Ang II receptors in the pathogenesis of TCAD and support a novel concept that TCAD may have its origin in the donor per se and may be modulated by the recipient's inherent biological factors.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   Ang II = angiotensin II   AT1R = angiotensin II type 1 receptor   AT2R = angiotensin II type 2 receptor   CMIT = changes in maximal intimal thickness   CPV = changes in plaque volume   HBSS = Hank's balanced salt solution   IVUS = intravascular ultrasound   mRNA = messenger ribonucleic acid   RAS = renin-angiotensin system   RNA = ribonucleic acid   RT-PCR = reverse transcription-polymerase chain reaction   TCAD = transplant coronary artery disease   vWF = von Willebrand factor