Abstract | BACKGROUND:
Pravastatin when administered with cyclosporine (CsA) has been shown to ameliorate transplant vasculopathy in the clinical setting. Previously we showed that pravastatin prevents chronic rejection in rat cardiac and liver transplant models. Here we determine whether pravastatin prevents chronic rejection in a rat renal allograft model. METHODS: Orthotopic renal transplantations were performed using Fisher 344 rats as donors and Lewis rats as recipients. Recipients were treated with low-dose CsA for 10 days to prevent acute rejection. Recipients were divided into three groups: CsA, CsA + pravastatin, and syngeneic. Renal function was assessed by serum creatinine level at day 130. Allografts were evaluated by histology and immunohistochemistry. Serum levels of alloantibodies were measured by flow cytometry. Intragraft cytokine mRNA expression was determined by semiquantitative reverse transcriptase-polymerase chain reaction. Intragraft levels of the antiapoptotic Bag-1 gene were measured by Western blot. RESULTS: CONCLUSION: This study demonstrates the ability of pravastatin to inhibit chronic rejection in rat renal allografts. Pravastatin's pleiotropic effects of reducing intragraft inflammatory cytokines, inhibiting immune cell infiltration, and causing up-regulation of the antiapoptotic gene Bag-1 suggest that its ability to prevent transplant chronic rejection may be multifactorial.
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Authors | Ping Ji, Ming-Sing Si, Yale Podnos, Helen Chow, Earl Steward, David K Imagawa |
Journal | Transplantation
(Transplantation)
Vol. 74
Issue 6
Pg. 821-7
(Sep 27 2002)
ISSN: 0041-1337 [Print] United States |
PMID | 12364863
(Publication Type: Journal Article)
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Chemical References |
- BCL2-associated athanogene 1 protein
- Carrier Proteins
- Cytokines
- DNA-Binding Proteins
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Immunoglobulin G
- Immunoglobulin M
- Isoantibodies
- Transcription Factors
- Pravastatin
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Topics |
- Animals
- Carrier Proteins
(genetics)
- Chronic Disease
- Cytokines
(biosynthesis, genetics)
- DNA-Binding Proteins
- Graft Rejection
(prevention & control)
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Immunoglobulin G
(blood)
- Immunoglobulin M
(blood)
- Isoantibodies
(blood)
- Kidney
(pathology, physiology)
- Kidney Transplantation
(immunology)
- Male
- Pravastatin
(therapeutic use)
- Rats
- Rats, Inbred F344
- Rats, Inbred Lew
- Transcription Factors
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