Therapeutic targets in liver transplantation: Angiotensin II in nonsteatotic grafts and angiotensin-(1-7) in steatotic grafts

I. Alfany-Fernandez, A. Casillas-Ramirez, M. Bintanel-Morcillo, K. B. Brosnihan, C. M. Ferrario, A. Serafin, A. Rimola, J. Rodés, J. Roselló-Catafau, C. Peralta

    Research output: Contribution to journalArticleResearchpeer-review

    23 Citations (Scopus)

    Abstract

    Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1-7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1-7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1-7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1-7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1-7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1-7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1-7), which is specific for steatotic liver grafts. © 2009 The American Society of Transplantation and the American Society of Transplant Surgeons.
    Original languageEnglish
    Pages (from-to)439-451
    JournalAmerican Journal of Transplantation
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2009

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