Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

Chihiro Suzuki, Masafumi Takahashi, Hajime Morimoto, Atsushi Izawa, Hirohiko Ise, Minoru Hongo, Yasushi Hoshikawa, Takayuki Ito, Hiroshi Miyashita, Eiji Kobayashi, Kazuyuki Shimada, Uichi Ikeda

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Abstract

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

Original languageEnglish
Pages (from-to)781-788
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number2
DOIs
Publication statusPublished - 20-10-2006

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Suzuki, C., Takahashi, M., Morimoto, H., Izawa, A., Ise, H., Hongo, M., Hoshikawa, Y., Ito, T., Miyashita, H., Kobayashi, E., Shimada, K., & Ikeda, U. (2006). Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. Biochemical and Biophysical Research Communications, 349(2), 781-788. https://doi.org/10.1016/j.bbrc.2006.08.109