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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Anticholesteremic Agents, CD28 Antigens, Graft Rejection, Heart, Heart Transplantation, Lymphocyte Function-Associated Antigen-1, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Myocardium, Simvastatin, Transplantation, Homologous.
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Does simvastatin prevent acute cardiac allograft rejection in CD28-deficient mice? Context: Heterotopic cardiac transplantation in mice was used to determine whether complementary immunomodulation by statins prevents lymphocyte function-associated antigen (LFA)-1-dependent acute allograft rejection in vivo. Hearts from BalbC mice were transplanted to the cervical vessels of either C57BL/6, CD11a(-/-), CD28(-/-) or double-deficient animals lacking expression of both LFA-1 and CD28. Allografts were rejected at days 7.2 +/- 0.7, 9.1 +/- 0.6 and 10.3 +/- 1.2 in C57BL/6, CD11a(-/-) and CD28(-/-) recipients, respectively. In contrast, mean allograft survival time in double-deficient animals was 27.2 +/- 2.9 days, indicating that acute allograft rejection in CD28(-/-) recipients was critically dependent on LFA-1 function. Allograft rejection was not delayed in CD28(-/-) recipients treated daily with 1 or 40 mg/kg simvastatin, graft survival was 9.6 +/- 0.2 and 10.3 +/- 0.3 days in these animals. Histology revealed that all rejected allografts uniformly presented with high-grade parenchymal rejection.
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Targeting of both LFA-1 and CD28 may provide efficient inhibition of co-stimulation and thus prolong experimental cardiac allograft survival. Simvastatin is not effective to blunt LFA-1-dependent acute cardiac allograft rejection in CD28(-/-) mice. Thus, pharmacological antagonism of LFA-1 function by oral treatment with statin compounds has to be considered an unsatisfactory means to improve the outcome after cardiac transplantation. Final Decision: no