Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

Journal Article · Fri Oct 20 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.08.109· OSTI ID:20854531

Suzuki, Chihiro ^[1]; Takahashi, Masafumi ^[1]; Morimoto, Hajime ^[1]; Izawa, Atsushi ^[1]; Ise, Hirohiko ^[1]; Hongo, Minoru ^[2]; Hoshikawa, Yasushi ^[3]; Ito, Takayuki ^[4]; Miyashita, Hiroshi ^[4]; Kobayashi, Eiji ^[5]; Shimada, Kazuyuki ^[4]; Ikeda, Uichi ^[1]

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1. Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto (Japan)
2. Department of Cardiovascular Medicine, Shinshu University School of Health Sciences, Matsumoto (Japan)
3. Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai (Japan)
4. Department of Cardiovascular Medicine, Jichi Medical School, Tochigi (Japan)
5. Division of Organ Replacement Research, Jichi Medical School, Tochigi (Japan)

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.

• OSTI ID: 20854531
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 349; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
ARTERIES
CELL PROLIFERATION
DEATH
ENDOTHELIUM
HYPERTENSION
HYPERTROPHY
IN VITRO
INFLAMMATION
MACROPHAGES
MAST CELLS
MAXIMUM PERMISSIBLE ACTIVITY
MUSCLES
POLYCYCLIC AROMATIC HYDROCARBONS
RATS