Mycophenolate mofetil prevents transplant arteriosclerosis by direct inhibition of vascular smooth muscle cell proliferation.
Abstract | UNLABELLED: METHODS: RESULTS: In the vehicle group, marked neointima formation was observed, with massive macrophages and T-cell infiltration in neointima, media, and adventitia. Marked expression of ET-1, PDGF-B, PDGFR-beta, TGFbeta1, and OPN were also observed in neointima. In the MMF40 and MMF20 groups, neointima formation was halted, but macrophages and T cells were infiltrated in the adventitia and adhered to the endothelium. In the MMF40 group, medial infiltration by macrophages and T cells and intimal expression of ET-1, PDGF-B, PDGFR-beta, TGFbeta1, and OPN was inhibited compared with the vehicle and MMF20 groups. Furthermore, MPA inhibited ET-1-induced VSMC proliferation but failed to inhibit its ERK1/2 activation. CONCLUSIONS: MMF treatment might have preventive potential in transplant patients with chronic vasculopathy through inhibition of VSMC proliferation.
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Authors | Hisashi Shimizu, Masafumi Takahashi, Shin-Ichi Takeda, Seiichiro Inoue, Jun Fujishiro, Yoji Hakamata, Takashi Kaneko, Takashi Murakami, Koichi Takeuchi, Izumi Takeyoshi, Yasuo Morishita, Eiji Kobayashi |
Journal | Transplantation
(Transplantation)
Vol. 77
Issue 11
Pg. 1661-7
(Jun 15 2004)
ISSN: 0041-1337 [Print] United States |
PMID | 15201664
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Endothelin-1
- Growth Substances
- Immunosuppressive Agents
- Mycophenolic Acid
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Topics |
- Animals
- Aorta, Abdominal
(pathology, transplantation)
- Aortic Diseases
(prevention & control)
- Arteriosclerosis
(prevention & control)
- Body Weight
(drug effects)
- Cell Division
(drug effects)
- Cells, Cultured
- Endothelin-1
(pharmacology)
- Growth Substances
(metabolism)
- Immunosuppressive Agents
(pharmacology)
- Macrophages
(drug effects, pathology)
- Male
- Muscle, Smooth, Vascular
(pathology)
- Mycophenolic Acid
(analogs & derivatives, pharmacology)
- Myocytes, Smooth Muscle
(pathology)
- Rats
- Rats, Inbred BN
- Rats, Inbred Lew
- Rats, Sprague-Dawley
- T-Lymphocytes
(drug effects, pathology)
- Tunica Intima
(drug effects, pathology)
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