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AEB-071 versus tacrolimus monotherapy to prevent acute cardiac allograft rejection in the rat: a preliminary report

 Y.H. Fang  ;  D.J. Joo  ;  B.J. Lim  ;  J.Y. Kim  ;  M.S. Kim  ;  H.J. Jeong  ;  Y.S. Kim 
 TRANSPLANTATION PROCEEDINGS, Vol.42(3) : 976-979, 2010 
Journal Title
Issue Date
Animals ; Graft Rejection/prevention & control* ; Graft Survival/drug effects ; Heart Transplantation/immunology* ; Heart Transplantation/physiology ; Lymphocyte Activation/drug effects ; Male ; Myocardial Contraction ; Pyrroles/therapeutic use* ; Quinazolines/therapeutic use* ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Tacrolimus/therapeutic use* ; Transplantation, Heterotopic/immunology ; Transplantation, Homologous
Inhibition of T-cell activation is the most efficient way to prevent transplant rejection. Protein kinase C (PKC) is an important signaling enzyme in the activation and regulation of T lymphocytes. AEB-071 (AEB) is a low-molecular-weight compound that blocks early T-cell activation via selective inhibition of PKC, a mechanism that differs from that of the calcineurin inhibitors. The present study sought to compare the effects of AEB versus tacrolimus (Tac) to prevent acute rejection in rats that had undergone heterotopic heart transplantation. We investigated the Brown Norway-Lewis rat strain combination for cardiac graft survival over 30 days after transplantation using varying doses of oral AEB and Tac monotherapy. Grafts were monitored by daily palpation; cessation of palpable ventricular contraction was considered to be rejection. Apart from necropsy, we performed histologic examinations of cardiac graft at 7 days after transplantation. In untreated recipients, allograft mean survival times (MST) was 6.83+/-0.41 days. AEB at 15, 30, or 60 mg/kg versus Tac at 1.2 mg/kg significantly prolonged graft survival to a MST of 12.33+/-1.21, 16.67+/-1.21, and 19.33+/-3.83, versus 17.00+/-6.90 days, respectively. Histologic assessment at 7 days after transplantation showed that high-dose AEB significantly decreased the histologic rejection score, indicative of decreased inflammatory cell infiltration into the graft. These results suggested that the administration of AEB (medium or high-dose), a PKC inhibitor, mitigated acute rejection and displayed significantly longer MST, similar to high-dose Tac after heterotopic heart transplantation in the rat.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Kim, Joon Ye(김준예)
Fang, Yu Hui(방우휘)
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
Jeong, Hyeon Joo(정현주) ORCID logo https://orcid.org/0000-0002-9695-1227
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
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