Systemic up-regulation of angiotensin II type 1 receptor in cardiac donors with spontaneous intracerebral hemorrhage

Mohamad H. Yamani, Daniel J. Cook, E. Murat Tuzcu, Ashraf Abdo, Philip Paul, Norman B. Ratliff, Yang Yu, Mohammad Yousufuddin, Jing Feng, Robert Hobbs, Gustavo Rincon, Corinne Bott-Silverman, Patrick M. McCarthy, James B. Young, Randall C. Starling

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Donor spontaneous intracerebral hemorrhage (ICH) is a potential risk factor for morbidity and mortality after cardiac transplantation. We hypothesized that donor ICH is associated with systemic up-regulation of angiotensin II receptor type 1 (AT1R). We evaluated mRNA expression of AT1R and AT2R in donor spleen lymphocytes and in heart biopsies from 20 recipients of hearts from donors with spontaneous ICH which were compared with 20 recipients from trauma donors. Heart biopsies showed 4.7-fold increased mRNA expression of AT1R (p < 0.0001) in the ICH group compared with the Trauma group. The ICH group also showed 2.6-fold (p < 0.01) increased mRNA expression of AT1R in the donor spleen lymphocytes, suggesting the presence of systemic activation before transplantation. At 1 year, the ICH group had increased coronary vasculopathy by vascular ultrasound. Using multivariate regression analysis, mRNA expression of AT1R in the donor spleen lymphocytes was found to be a strong independent predictor of transplant vasculopathy (odds ratio = 4.397, CI = 1.243-15.553, adjusted p = 0.02). This is the first report to describe splenic up-regulation of AT1R in the presence of spontaneous ICH and its association with subsequent development of transplant vasculopathy.

Original languageEnglish (US)
Pages (from-to)1097-1102
Number of pages6
JournalAmerican Journal of Transplantation
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2004

Keywords

  • Angiotensin II receptors
  • Heart transplantation
  • Spontaneous intracerebral hemorrhage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Yamani, M. H., Cook, D. J., Tuzcu, E. M., Abdo, A., Paul, P., Ratliff, N. B., Yu, Y., Yousufuddin, M., Feng, J., Hobbs, R., Rincon, G., Bott-Silverman, C., McCarthy, P. M., Young, J. B., & Starling, R. C. (2004). Systemic up-regulation of angiotensin II type 1 receptor in cardiac donors with spontaneous intracerebral hemorrhage. American Journal of Transplantation, 4(7), 1097-1102. https://doi.org/10.1111/j.1600-6143.2004.00463.x